CCR7 Central and CCR7 Effector Memory CD4 T Cells in Human Cutaneous Leishmaniasis.

Purpose: The profile of central (=T) and effector (=T) memory CD4 T cell subsets and the possible role as surrogate markers of protection is studied in the volunteers with history of cutaneous leishmaniasis (HCL). Methods: Profile of T cell subsets based on CCR7/CD45RA expressions and phenotypic changes after soluble Leishmania antigen (SLA) stimulation were analyzed. Then, sorted CD4CD45ROCD45RA naïve T, CD4CD45ROCD45RACCR7 T CD4CD45ROCD45RACCR7 T subsets were cultured with SLA for proliferation, cytokine production and intracellular cytokine assays. Results: In the HCL and control volunteers, the mean frequencies of CD4CD45RACCR7 naïve T cells and CD4CD45RACCR7 T cells were higher than the other subsets before culture. Frequency of naïve T cells and CD4CD45RACCR7 T cells was significantly decreased ( P = 0.01 for naïve T and P < 0.05 for T cells) and frequency of T cells was significantly increased after SLA stimulation compared to before culture ( P < 0.001). By CFSE labeling, CD4CD45ROCD45RACCR7 T cells showed more proliferation potential than CD4CD45ROCD45RACCR7 T cells. Stimulation of the T cells in HCL volunteers induced a significantly higher IFN-γ production ( P = 0.04) with higher number of intracellular IFN-γ positive cells ( P = 0.032) than the same cells from controls. A significantly higher number of T cells produced IL-2 in HCL volunteers compared with controls ( P < 0.05). Most of the intracellular IFN-γ positive T cells were proliferating CFSE-dim populations ( P < 0.05). Conclusions: A combination of Leishmania-reactive IFN-γ producing CD4CD45ROCD45RACCR7 T and Leishmania-reactive IL-2 producing CD4CD45ROCD45RACCR7 T are identified in individuals with history of CL which might play a role in protective recall immune response against Leishmania infection. [ABSTRACT FROM AUTHOR]