CD4+CD25+ regulatory T cells restrain pathogenic responses during Leishmania amazonensis infection.
Although activation of CD4(+) T cells mediates pathogenesis in Leishmania amazonensis (La)-infected mice, these susceptible mice do not develop a polarized Th2 response, suggesting a unique mechanism of disease susceptibility. To understand how Th cell activities are regulated, we examined the frequency and phenotypes of regulatory T (Treg) cells. At 1-3 wk of infection, relatively high percentages of CD4(+)CD25(+)CD86(+) T cells, as well as high levels of FoxP3, TGF-beta1, and IL-10RI transcripts, were detected in the skin and draining lymph nodes, indicating local accumulation of Treg cells. Lesion-derived, IL-10-producing CD4(+)CD25(+) cells effectively suppressed proliferation and cytokine (IL-2 and IFN-gamma) production of CD4(+)CD25(-) effector cells. Adoptive transfer of lesion-derived CD4(+)CD25(+) cells to syngeneic, naive C57BL/6 mice before infection significantly reduced disease development. To further validate the beneficial role of Treg cells in La infection, we adoptively transferred CD25(+) T cell-depleted splenocytes (derived from naive mice) into RAG1(-/-) mice. This transfer rendered RAG1(-/-) mice more susceptible to La infection than the mice receiving control splenocytes. The beneficial effect of Treg cells was transitory and correlated with decreased activation of IFN-gamma-producing effector T cells. This study uncovers an intriguing role of Treg cells in restraining pathogenic responses during nonhealing Leishmania infection and emphasizes a balance between Treg and Th1-like effector cells in determining the outcome of New World cutaneous leishmaniasis.
Ji
Jiaxiang
J
Department of Microbiology and Immunology, Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, 77555, USA.
Masterson
Joseph
J
Sun
Jiaren
J
Soong
Lynn
L
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000469:parasitology; D018450:Disease Progression; D005260:Female; D016130:Immunophenotyping; D007894:Leishmania mexicana / Q000276:immunology* / Q000472:pathogenicity*; D016773:Leishmaniasis, Cutaneous / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D018655:Lymphocyte Count; D008212:Lymphocyte Depletion; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000469:parasitology; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism / Q000469:parasitology / Q000473:pathology / Q000637:transplantation*
D015375:Receptors, Interleukin-2