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. As antiretroviral therapy leads to an increase in memory T cells 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+). 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].