Here we developed the first mathematical model of peripheral Treg-cell homeostasis, incorporating secondary lymphoid organs as separate entities and encompassing factors determining the size of the Treg-cell

population, namely thymic output, homeostatic proliferation, peripheral conversion, transorgan migration, apoptosis, and the Tnaive-cell population. Quantitative data were collected by monitoring Tnaive-cell homeostasis and Treg-cell rebound after selective in vivo depletion of Treg cells. Our model predicted the previously unanticipated possibility that Treg cells regulate migration of Tnaive cells between spleen and peripheral lymph nodes (LNs), whereas migration learn more of Treg cells between Ipilimumab mouse these organs can largely be neglected. Furthermore, our simulations suggested that peripheral conversion significantly contributed to the maintenance of the Treg-cell population, especially in LNs. Hence, we provide the first estimation of the peripheral Treg-cell conversion rate and propose additional facets of Treg-cell-mediated

immune regulation that may previously have escaped attention. “
“Stimulation of neutrophils may potentiate immunity to Leishmania major. CpG-containing oligodeoxynucleotide (ODN) has immune stimulatory effects and has been suggested as adjuvants and therapeutics to potentiate efficacy of vaccines and treatments against leishmaniasis. Here, we examined the stimulatory effect of synthetic ODN containing CpG motifs class A and

B on cytokine production by neutrophils. Neutrophils from healthy donors responded to CpG-ODN type A, but not to class B, with secretion of IL-8 and following GM-CSF pretreatment with TNF-α production. To test whether neutrophil responses were altered in cutaneous leishmaniasis (CL) and to better understand the role of neutrophils in susceptibility and resistance to disease, we evaluated cytokine responses in GM-CSF preconditioned O-methylated flavonoid neutrophils from asymptomatic (Leishmanin skin test positive, LST+) and nonhealing CL individuals to CpG-ODN class A and assessed the expression levels of toll-like receptors (TLR2), 4 and 9. LST+ and healthy donor, but not nonhealing CL neutrophils, responded with TNF-α secretion. Neutrophils from nonhealing CL displayed increased mRNA expression levels of TLR2, 4 and 9 compared to neutrophils from LST+ or healthy donors. Therefore, failure to cure CL is associated with reduced ability of neutrophils to secrete TNF-α and correlates with high TLR 2, 4 and 9 expressions. Cutaneous leishmaniasis (CL) is a widespread and highly endemic disease in young individuals in many parts of the Middle East and central Asia. There is no effective vaccination, and control of disease relies primarily on chemotherapy, which is expensive and can have major side effects (1) and in addition may not reduce the stigmatizing features of CL.