IgG concentrations prior to and at the time of rituximab

correlated with nadir IgG. IgG replacement was initiated because of recurrent infection in 12 (4.2%) patients and a lower IgG increased the odds ratio of receiving IgG replacement. IgG replacement therapy decreased the incidence and severity of infections, and recovery of IgG concentrations allowed cessation of IgG replacement in two patients after 4 and 7.5 years of replacement treatment. Conclusions: Monitoring of IgG is recommended for patients receiving rituximab. IgG replacement for sustained hypogammaglobulinaemia with recurrent BI2536 infections appears effective. The IgG treatment course is prolonged in most patients, but IgG recovery is reported. 175 PARENTAL PERSPECTIVES ON THE FINANCIAL IMPACT OF CARING FOR A CHILD WITH CHRONIC KIDNEY DISEASE M MEDWAY1,2, learn more A TONG1,2, JC CRAIG1,2,

S KIM2, F MACKIE3, S MCTAGGART4, B BARTON5, K HOWARD1, G WILLIAMS1,2, A WALKER6, G WONG1,2 1Sydney School of Public Health, The University of Sydney, Sydney, NSW; 2Centre for Kidney Research, The Children’s Hospital at Westmead, Sydney, NSW; 3Department of Nephrology, Sydney Children’s Hospital, Sydney, NSW; 4Department of Nephrology, Royal Children’s Hospital, Brisbane, QLD; 5Children’s Hospital Education Research Institute, The Children’s Hospital at Westmead, Sydney, NSW; 6Department of Nephrology, Royal Children’s Hospital, Melbourne, Victoria, Australia Aim: This study aims to describe parental perspectives on the financial impact of caring for a child with CKD. Background: Chronic kidney disease (CKD) can impose a significant social

and financial burden on patients and caregivers, however little is known about how caregivers experience and cope with the financial impact of CKD. Methods: Face-to-face semi-structured interviews were conducted with 27 parents of children with CKD across three centres in New South Wales and Queensland. Transcripts were thematically analysed. Results: We identified five themes: loss of freedom (prioritizing demands of care, limiting occupational opportunities, appreciating socio-economic advantage); burden of sole responsibility (inability to rely Suplatast tosilate on others, lack of respite, increased separation of family roles, self-reliance); adapting for survival (vigilant budgeting, redefining normality and expectations, rechanneling resources to basic needs, exploring new income sources, negotiating work flexibility); instability of circumstances (depleted capacity to work, unpredictability of child’s health, burden of travel-related costs, imposition of debt, domestic upheaval); and struggle in seeking support (‘falling through the cracks’, unmet information needs). Conclusions: Parents experienced meeting the complex needs of their child with CKD as an overwhelming focus, which they believed consumed much of their resources, time and energy.

Further, does the in vitro context of Th cell polarization recapitulate the potential variation of ERF activation downstream of TCR signalling

in vivo? For example, increased TCR signal strength can affect mature T-cell polarization (biasing towards Treg and Th17 cell lineages), and one possibility is that signal strength differences result in dosage effects of TCR-associated transcription factors, such as AP-1, IRF4 and NFAT, with intended effects on target gene expression. Furthermore, it will be important to better understand the differences in chromatin states and transcription factor function in initial polarization compared with long-term maintenance of T-cell subsets. Whereas description of enhancer characteristics is extensive – chromatin accessibility, H3K4me1, H3K27ac, p300 recruitment, physical interaction LY294002 chemical structure with promoters – it will be exciting

to learn more about the precise mechanisms of enhancer-mediated activation of transcription. Finally, we have much to learn about the graded, sequential progression of regulatory chromatin ‘maturation’, from condensed, to poised, to fully active, with augmentation R788 mw of associated gene transcription, and the specific roles of DNA- and chromatin-binding factors in this process. I appreciate ongoing support and mentorship from C. David Allis. I thank A.Y. Rudensky and members of the Allis and Rudensky laboratories for helpful discussions, and M. Sellars, A. Arvey, C. Li and R. Niec for insightful comments and input on the manuscript. S.Z.J. is supported by the National Institutes of Health

under Ruth L. Kirschstein National Research Service Award (GM100616). The author declares no conflict of interest. “
“Department of Immunobiology, Division of Immunology, Infection and Inflammatory Diseases, King′s College London, London, UK College of Life Sciences, ifenprodil University of Dundee, Dundee, UK Type 1 diabetes results from destruction of insulin-producing beta cells in pancreatic islets and is characterised by islet cell autoimmunity. Autoreactivity against non-beta cell-specific antigens has also been reported, including targeting of the calcium-binding protein S100β. In preclinical models, reactivity of this type is a key component of the early development of insulitis. To examine the nature of this response in Type 1 diabetes, we identified naturally processed and presented peptide epitopes derived from S100β, determined their affinity for the HLA-DRB1*04:01 molecule and studied T cell responses in patients, together with healthy donors. We found that S100β reactivity, characterized by IFN-γ secretion, is a characteristic of Type 1 diabetes of varying duration.

89,90 Like other B7 family members, B7-H3 mRNA is broadly expressed, but protein expression is restricted. B7-H3 protein can be detected on human myeloid DCs but can only be detected following induction Apoptosis inhibitor with inflammatory stimuli in other leukocyte populations in both humans and mice.87,91,92 The triggering receptor expressed on myeloid cells (TREM)-like transcript 2 (TLT-2) has been identified as a stimulatory counter receptor for B7-H3 on T cells, although this finding is controversial.93,94 Studies with B7-H3-deficient mice support an inhibitory function for B7-H3, displaying elevated T-cell responses in several experimental

settings.91 B7-H3 also appears to have an important function outside the immune system, as B7-H3-deficient mice exhibit reduced bone strength

because of impaired osteoblast differentiation.95 In relation to pregnancy, B7-H3 ICG-001 expression is observed in the villous placenta and changes with advancing gestation, starting within the mesenchymal cells of villi early, and shifting to the syncytiotrophoblast by term.86 The role of B7-H3 in pregnancy is unknown. B7-H4 is another B7 family protein that has been shown to exhibit negative costimulatory activity on T cells, including inhibiting proliferation and cytokine production.96,97 As with the other B7 family members, B7-H4 mRNA is widely distributed, including in human placenta.96 B7-H4 protein expression appears to be restricted to activated hematopoietic cells in humans, but murine B cells constitutively express B7-H496,97 Casein kinase 1 Although the CD28 family member B and T lymphocyte attenuator (BTLA) was initially proposed as a counter-receptor for B7-H4, this no longer seems likely as herpes virus entry mediator (HVEM) is now considered the unique ligand for BTLA.98 T cells express the unknown receptor for B7-H4 following activation.96,97 Studies using B7-H4-deficient

mice suggest that B7-H4 suppresses Th1 immune responses and also inhibits expansion of neutrophils from their progenitors.99,100 Reverse signaling through B7-H4 has also been reported in EBV-transformed B cells, resulting in upregulation of FasL and subsequent apoptosis.101 The role of B7-H4 in pregnancy has not been addressed; however, B7-H4 has been detected on decidual macrophages from term decidua basalis by flow cytometry102 and may therefore potentially affect pregnancy in some manner. B7-H6 is the newest member to the B7 family. It is an activating ligand for the NK receptor, NKp30, and appears to be involved in inducing NK lysis of tumor targets.103 Expression of B7-H6 appears to be highly restricted to tumor cells. In contrast to other B7 family members, B7-H6 mRNA was not detected in any normal tissues, and surface protein expression was absent on both freshly isolated and activated PBMCs.

Both types of memory B cells consistently upregulate the orphan receptor EBI-2 (T. Kaji and T. Takemori, unpublished), allowing them

to migrate into the outer B cell follicle [11]. However, it remains uncertain whether GC-independent memory B cells develop at the border of T- and B-cell zones or in the follicle. Although T-cell CXCR5 is needed for optimal GC responses, CXCR5-deficient PARP inhibitor T cells are able to access follicles and induce GCs, albeit smaller in size compared with wild-type T cells [36, 40]. Likewise, a small number of GC B cells were generated in the spleen of mice in the absence of TFH cells at day 7 after immunization [2], raising the possibility that non-TFH cells may also access follicles and help B cells to respond at an early stage of the immune response. TFH cells secrete IL-21 [41]. IL-21 signaling profoundly affects GC function by promoting the proliferation of GC B cells and their differentiation into memory B cells. Accordingly, in mice deficient for IL-21, memory B cells exhibit lower levels

of somatic mutations in rearranged Ig V region genes compared with memory B cells from wild-type controls [8]. There is no specific cell surface marker known for memory B cells, although PD-L1, PD-L2, CD35, CD80, and ecto-5′-nucleotidase CD73 have CX-5461 been reported to be expressed on memory B cells in the spleen in contrast to naïve B cells [26] or naïve and GC B cells [42]. Along these lines, we have confirmed that the levels

of PD-L2 and CD80 expression are significantly increased in both GC-independent and -dependent memory B cells compared with those in naïve and GC B cells [2] (Fig. 1). However, as previously reported [9], CD73 is expressed on GC B cells and a subset of memory B cells in wild type mice as the immune response progresses. On GC-independent memory B cells, CD73 is expressed at a low level. In our study, approximately 80% of CD73+ memory B cells in wild-type mice carried somatically mutated Ig V region gene segments [2]. Thus, CD73 expression may preferentially mark somatically mutated memory cells. Although we observed costimulatory MHC class II, CD40, and CD80 molecules to be almost why equally expressed on both day 7 and day 40 GC-independent and -dependent memory B cells, the cell surface expression level of PD-L2 increased from day 7 to day 40 after immunization on both types of cells [2]. Thus, GC-independent and -dependent memory cells express several common surface markers at comparable levels, except for CD73. The memory B-cell population consists of clones that have proliferated in response to an antigen and then remain in a resting state for a long period of time [23]. Their survival is independent of T-cell help and of continuous contact with cognate antigen [43, 44]. It has been suggested that memory B cells localize in spleen and other secondary lymphoid organs [26], and also circulate in blood [6].

Central to DC functioning is their ability to take up antigens. To directly compare the endocytic activity of MoDCs and BDCs, we examined their uptake of FITC-dextran over time from day 0 to day 7. The ability to take up FITC-dextran increased from 29 ± 30% (mean ± SD) on day 1 to 58 ± 24%

on day 4 and 57 ± 27% on day 6. In contrast, 16 ± 18% of BDCs on day 1 were endocytically active following their Epigenetics inhibitor isolation from blood. Laser confocal microscopy confirmed the uptake of particles of FITC-dextran in both MoDCs and BDCs (data not shown). Overall, these results show that BDCs were consistently less endocytic than MoDCs. As DCs mature, the expression of co-stimulatory molecules such as CD80 or CD86 increases providing DCs with the ability to activate T cells. Furthermore, up-regulation of the chemokine receptor CCR7 allows DCs to migrate to the lymph node where they encounter lymphocytes.19 To compare the expression of co-stimulatory molecules and CCR7 within each DC population, MoDCs and BDCs were stimulated with LPS (100 ng/ml) for 24-hr. Flow cytometric analysis showed that CD80/86 expression increased from 46% to 67% (median) in MoDCs (stimulation index = 1·5) (Fig. 2a; P < 0·05), and from 14% to 45% in BDCs (stimulation index = 3·8) (Fig. 2b; P < 0·05) as determined by flow cytometry. Within the 6-hr stimulation with LPS, CCR7 gene expression increased by 3·4-fold (median)

in BDCs and 2·0-fold in MoDCs (Fig. 3). In summary, MK-2206 nmr in response to stimulation with LPS both MoDCs and BDCs demonstrated the characteristics of mature DCs in terms of co-stimulatory molecule cell surface expression and CCR7 gene expression. At sites of injury, DCs release

chemokines that are involved in recruiting innate and adaptive immune cells. The ability of DCs to produce chemokines was examined following a 6-hr stimulation with LPS. Over fourfold up-regulation was observed in CCL-4, CCL-20 and CXCL2 SB-3CT gene expression in both MoDCs and BDCs (Fig. 4a) with the up-regulation observed to be higher in BDCs for all of the genes examined. In BDCs, there was also CCL-2 up-regulation. In lymph nodes, DCs interact with T cells by delivering different types of signals including cytokines. The expression of cytokines in MoDCs and BDCs was compared by qRT-PCR following a 6-hr stimulation with LPS. No changes were observed in IFN-α and IFN-γ, whereas a greater than threefold up-regulation was observed in IL-12 in BDCs and in IL-6, IL-8 and TNF-α in both MoDCs and BDCs (Fig. 4b). No IL-12 was detected in MoDCs. Cytokine secretion was examined by ELISA following a 24-hr stimulation with LPS. Production of IL-6, IL-8, IL-12 and TNF-α was significantly increased in BDCs (Table 3). Expression of IL-6, IL-8 and TNF-α was increased in MoDCs although the change was not statistically significant. Higher baseline values (control) were observed in MoDCs compared with BDCs.

Furthermore, Foxo1f/fCd19Cre mice had markedly fewer LN B cells and an increase in peripheral blood B cells (Supporting Information Fig. 1D). The paucity of LN B cells correlated with reduced surface expression of CD62L (L-selectin), the LN homing receptor (Supporting Information Fig. 1E). The mice also had a reduced percentage of CD5+ B cells in the peritoneal cavity (Supporting Information Fig. 1F). The report from Dengler et al. did not examine the developmental status or function of peripheral B220+IgM+ cells in Foxo1f/fCd19Cre mice 10. We stained splenocytes from our Foxo1f/fCd19Cre mice and

controls with antibody combinations that distinguish two mature subsets (FO, MZ) and four transitional Anti-infection Compound Library concentration B-cell subsets (T1, T2, T3 and MZ precursor (MZP)) 13. When compared with control Foxo1f/+Cd19Cre mice, Foxo1f/fCd19Cre mice displayed a consistent and statistically significant increase in the percentage of MZ cells, defined as B220+AA4.1−IgMhiCD21hiCD23lo (Fig. 1A). In contrast, the percentage of FO cells (B220+AA4.1−IgMloCD21intCD23hi) was reduced (Fig. 1A). A normal percentage of MZP cells was present in Foxo1f/fCd19Cre mice, despite reduced percentages of T1 and T2 cells; this suggests that immature transitional cells might commit preferentially to the MZP stage. The absolute numbers of splenocytes were equivalent between Foxo1f/fCd19Cre mice and control mice (data not shown). Increased abundance of B220+ cells

in the splenic MZ and other extrafollicular regions https://www.selleckchem.com/products/ulixertinib-bvd-523-vrt752271.html was also apparent by immunofluorescent staining of spleen sections (Fig. 1B). The

percentages of mature FO and MZ cells were comparable in the two control groups (Foxo1f/+Cd19Cre and Foxo1f/f) (Fig. 1A), and other experiments showed a consistently greater population of MZ cells (B220+CD21hiCD23lo) in Foxo1f/fCd19Cre compared with Foxo1f/f mice (data not shown). Therefore, we used Foxo1f/f mice as controls in Fig. 1B and in other experiments to simplify breeding schemes. The altered balance of FO and MZ cells in Foxo1f/fCd19Cre mice Carbohydrate was not observed in analyses of mice with Foxo1-deficient B cells generated using Cd21Cre10. A likely explanation is that Cd21Cre drives deletion of Foxo1 at a time point after transitional B cells commit to either the FO or the MZ lineage, whereas Cd19Cre deletion is complete by this stage. Interestingly, Foxo1f/fCd21Cre mice 10 shared the reduced LN B-cell population and CD62L expression observed here in Foxo1f/fCd19Cre mice. This could be explained by a requirement for Foxo1 in CD62L gene expression in mature B cells, after Cd21Cre-mediated deletion is completed. We purified splenic B cells and activated them in vitro with titrated doses of either a BCR stimulus (anti-IgM) or a TLR stimulus (LPS). We measured cell proliferation and survival by cell division tracking using CFSE. B cells from Foxo1f/fCd19Cre proliferated more weakly to anti-IgM, compared with B cells from Foxo1f/f mice (Fig. 2A).

In-vitro differentiative potential of MSCs is not restricted

to mesodermal lineages, but their transdifferentiation into other lineages, such as endothelia, could be realized Mitomycin C cost both in vitro and in vivo [5]. In addition, MSCs exhibit immunoregulatory activities, inhibiting the function of different immune cells of innate and adaptive immunity [6], blocking the division of stimulated T cells, preventing irreversible G0/G1 phase arrest and stopping T cell division in mixed lymphocyte reactions (MLRs) [7]. However, the immunomodulatory activity of the MSCs does not rely solely upon T cells, but also upon the first step of the immune response through the inhibition of dendritic cell differentiation and maturation in antigen-presenting cells [8]. Furthermore, their regulatory activity may be amplified by modulating immune responses via the de-novo induction and expansion of CD4+CD25+forkhead box protein 3 (FoxP3)+ regulatory T cells (Tregs). Tregs play a critical role in peripheral self-tolerance, as well as in the regulation of acquired immunity, by inhibition of lymphocyte proliferation [9, 10]. As well as Tregs developing in the

thymus (natural Tregs), a Treg population can be induced from peripheral naive www.selleckchem.com/products/poziotinib-hm781-36b.html T cell (inducible Tregs), and these inducible Tregs can be recruited directly by MSC from CD4+ T cells [11, 12]. In recent decades many studies have been published addressing the role of Treg number and function in human autoimmunity [13], suggesting that their possible defective function plays a role in many autoimmune diseases. On this basis, both the regenerative and the immunomodulatory properties of MSCs make them an attractive candidate crotamiton for cellular therapy in autoimmune diseases. Systemic sclerosis (SSc) is an autoimmune disease in which alteration of cellular immunity, including T and B lymphocytes, has been largely

studied both in the skin and in internal organs [14, 15]. Furthermore, recent evidence has shown an aberrant dendritic cell function in SSc, contributing to the molecular milieu of the disease [16]. We have shown previously that MSCs obtained from SSc patients (SSc–MSC) were normal with respect to clonogenicity and differentiative capacity, although they displayed early senescence and were defective in acquiring some differentiative functions [17]. Senescent MSC generally show a flattened morphology, over-expression of senescence-associated β-galactosidase (β-Gal) activity, reduced telomerase activity and increased expression of both p53 and p21, which are negative regulators of cell proliferation [18]. At present, only few papers have investigated the immunoregulatory activity in SSc.

Consistent with this finding,

Balboa et al. [21] report that p38 is hyperphosphorylated in CD16+ monocytes from TB patients, which may explain their reduced capacity to differentiate into DCs. In more general terms, the higher frequency of CD16+ monocytes observed in TB patients still has to be understood because high CD16 frequency is also characteristic of other infectious and noninfectious inflammatory conditions. On the one hand, it would be of interest to examine whether the shift in the monocyte population toward a CD16+ subset, along with the hyperactivation of p38 MAPK, might be dependent on the RD-1 (region of difference-1) virulence locus [28]. Indeed, studies 3-deazaneplanocin A molecular weight may be carried out using nonpathogenic mycobacteria strains (e.g., Mycobacterium bovis bacille Calmette-Guerin) or mutants lacking this selleck chemicals llc region (i.e., H37∆RD1). On the other

hand, the predominance of the CD16+ monocyte subset in inflammatory conditions might rather reflect a host-driven protective response to limit the immunopathology caused by (chronic) infectious agents such as M. tuberculosis. Factors such as transforming growth factor TGF-β, known to induce CD16+ monocyte differentiation, are usually involved in the immunomodulation responses by the host to preserve tissue integrity. Interestingly, TGF-β is increased in the blood of TB patients [29, 30]. Based on the findings reported by Balboa et al. [21], it is tempting to conclude that CD16+ monocytes might be a cause for TB susceptibility rather than a consequence of it. To test this hypothesis, studies using in vivo depletion models [31] will be required to understand whether Ly6C+ monocytes, the equivalent to human CD16+ monocytes in the mouse, play a detrimental or beneficial role during TB. If their prominence in TB infection results in a significant decrease in the numbers

of DCs with the ability to efficiently activate adaptive immunity, then it might be predicted that the depletion of CD16+ monocytes would trigger a better T-cell response and better clearance of M. tuberculosis in infected hosts. By contrast, if CD16+ monocytes are essential to the generation of regulatory cells to protect against immunopathology, Bay 11-7085 then TB will result in lung tissue injury from uncontrolled inflammation in their absence. Whether or not any of the implications discussed above hold true, what is certain is that the current report by Balboa et al. [20] has brought us a step closer to solve the enigma of how M. tuberculosis impairs the Ag presentation process, and is likely to yield new avenues of investigation in monocyte development and the signaling pathways involved in their activation. We thank D. Hudrisier for critical evaluation of this manuscript.

78 After binding of the bacterial product lipopolysaccharide to Toll-like receptor 4, integrin Mac-1 (CD11b/CD18) could also be activated in macrophages. However, in contrast to the positive role of LFA-1 in T-cell activation, integrin Mac-1 plays a negative role to reduce Toll-like receptor-mediated signalling and limits inflammation.79 Further, new functions of integrins in leucocytes are emerging. Integrin α4β7 in mucosal T cells binds directly with the V2 loop of gp120 in HIV-1, which results in rapid activation of LFA-1 to facilitate the formation of virological learn more synapses and efficient cell-to-cell spreading of HIV-1. Blocking the interaction of integrin

α4β7 with gp120 via a peptide could significantly reduce HIV-1 entry into T cells.80 ITK, which regulates integrin activation, can enhance HIV-1 entry and transmission between cells.81 Integrin αEβ7 (CD103) has also been identified in regulatory T (Treg) cells but plays no mandatory role for Treg-cell-mediated control of colitis.82 Signalling proteins Rap1 and protein kinase C-θ (PKC-θ) which affect integrin activation

might regulate Treg-cell function.83,84 With more detailed understanding of the role of different integrins in different cell types, we would target specific integrins with blocking antibodies, RGD (arginine-glycine-aspartic acid) peptides or small molecules in the treatment of various diseases. For example, blocking antibody to α4-integrin has shown some degree of success in multiple sclerosis and in inflammatory bowel disease.9 However, there are some remaining concerns, including the possibility that blocking integrin www.selleckchem.com/products/acalabrutinib.html function ADP ribosylation factor would generally compromise the immune

system’s ability to fight against infection or that diseases might relapse upon cessation of blockade of integrins. It is therefore important to understand the underlying molecular mechanism of how integrin function is regulated, and this might provide us with new specific targets through which to treat integrin-related diseases. This work was supported by grants from the Ministry of Science and Technology of China (2011CB505005 and 2012CB910800), National Natural Science Foundation of China (31070778), the Chinese Academy of Sciences and Shanghai Science and Technology Committee (11PJ1410700). The authors have no conflicts of interest to disclose. “
“Matrix metalloproteinases are responsible for degradation and remodelling of extracellular matrix and exert important roles in initiation and progression of inflammatory diseases. We aimed to examine the role of Matrix metalloproteinases (MMPs) and their regulators in degenerative arterial diseases. Serum samples were collected from patients with arterial disease (n = 126), who underwent surgery because of symptomatic aorto-occlusive disease (AOD, n = 18), carotid artery stenosis (n = 67) or abdominal arotic aneurysm (n = 41).

4a,b; NS=42·77 (33·80–64·12) versus ML = 94·09 (46·72–97·90); P < 0·05]. In addition, cell frequency also increased in the ML-stimulated PBMC culture of RR/HIV patients

when compared with the HC and RR groups under the same conditions [Fig. 4a,b; HC = 15·35 (0·5–28·08), RR = 9·87 (4·50–38·08); P < 0·05]. The frequency of CD4+ CD25+/CD4+ T cells and CD8+ CD25+/CD8+ T cells Nivolumab clinical trial was not significantly modulated in any of these groups (data not shown). As leprosy is marked by a localized immune inflammation in skin lesions, the expression of these activation markers in the skin biopsies of the RR and RR/HIV patients was evaluated. Double-immune labelling was used to examine CD69 and CD38 activation markers in CD4+ and CD8+ T cells in RR and RR/HIV skin lesions. Both groups presented a dermal infiltrate consisting of numerous CD3+ CD4+ and CD3+ CD8+ T cells (data not shown). The percentage of CD4+ CD69+ cells found was similar in both the RR (50%) and RR/HIV (40–50%) lesions (Fig. 3c). In contrast, a greater percentage of

CD4+ T cells co-localizing with CD38 (40–50%) was observed among the RR/HIV patients. This pattern differed from the one seen in RR lesions in which only a few cells co-localized with CD38 (< 5%). RR/HIV dermal infiltrate also presented greater numbers of CD8+ CD69+ T cells than those found among the RR patients (Fig. 4c; RR 20% versus RR/HIV 50%), and of CD8+ CD38+ T cells (Fig. 4c; RR< 5% versus RR/HIV40–50%). Memory T cells are known to be more Selleckchem Erlotinib sensitive to antigenic stimuli than naive T cells and to mount a more rapid and broader pathogen-specific response.[25] As antiretroviral therapy leads to an increase in memory T cells[26] and all patients evaluated in this study were under HAART treatment, the next step was to evaluate the memory phenotype of the PBMCs of RR/HIV patients after ML in vitro stimulation via analysis of molecular surface expression of CD45RA and CCR7. In compliance with these parameters, T L-gulonolactone oxidase cells were classified as naive T cells (CCR7+ CD45RA+), central memory T cells (TCM; CCR7+ CD45RA−), effector memory T cells (TEM; CCR7− CD45RA−),

or TEMRA cells (CCR7– CD45RA+).[27] In ML-stimulated cultures, an increase in TCM CD4+ T-cell frequencies was observed in both the RR and RR/HIV groups [Fig. 5a,b; RR NS = 16·5 (10·2–23·20) versus ML = 22·5 (19·5–30·3); P < 0·05; RR/HIV NS = 10·8 (9·8–20·9) versus ML = 23·8 (16·15–36·1)]. The same profile was identified in relation to TCM CD8+ cell frequencies in the RR/HIV group alone [Fig. 5a–c; NS = 11·7 (7·8–18·9) versus ML = 20·40 (10·5–28·4); P < 0·05]. In this group, an increase in TEM CD8+ T cells was also seen in ML-stimulated cells in comparison to NS cells [Fig. 5a–c; NS = 16·4 (7·4–23·7) versus ML = 27·50 (22·3–43·3); P < 0·05] and also in comparison with ML-stimulated cells of the other groups evaluated [Fig. 5a–c; HC 10·88 (9·2–22·10); RR 15·17 (4·3–24·6); RR/HIV 27·4 (22·3–43·3); P < 0·05].