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Tracking antigen-specific CD4+ T cells throughout the course of chronic Leishmania major infection in resistant mice.
Title | Tracking antigen-specific CD4+ T cells throughout the course of chronic Leishmania major infection in resistant mice. |
Publication Type | Journal Article |
Year of Publication | 2013 |
Authors | Pagán, AJ, Peters, NC, Debrabant, A, Ribeiro-Gomes, F, Pepper, M, Karp, CL, Jenkins, MK, Sacks, DL |
Journal | Eur J Immunol |
Volume | 43 |
Issue | 2 |
Pagination | 427-38 |
Date Published | 2013 Feb |
ISSN | 1521-4141 |
Keywords | Animals, Antigen Presentation, Antigens, Protozoan, CD4-Positive T-Lymphocytes, Ear, Epitopes, T-Lymphocyte, Female, Forkhead Transcription Factors, Histocompatibility Antigens Class II, Interferon-gamma, Interleukin-10, Leishmania major, Leishmaniasis, Cutaneous, Mice, Mice, Inbred C57BL, Receptors, Antigen, T-Cell, Spleen, T-Lymphocytes, Regulatory, Th1 Cells |
Abstract | Primary Leishmania major infection typically produces cutaneous lesions that not only heal but also harbor persistent parasites. While the opposing roles of CD4(+) T-cell-derived IFN-γ and IL-10 in promoting parasite killing and persistence have been well established, how these responses develop from naïve precursors has not been directly monitored throughout the course of infection. We used peptide:Major Histocompatibility Complex class II (pMHCII) tetramers to investigate the endogenous, parasite-specific primary CD4(+) T-cell response to L. major in mice resistant to infection. Maximal frequencies of IFN-γ(+) CD4(+) T cells were observed in the spleen and infected ears within a month after infection and were maintained into the chronic phase. In contrast, peak frequencies of IL-10(+) CD4(+) T cells emerged within 2 weeks of infection, persisted into the chronic phase, and accumulated in the infected ears but not the spleen, via a process that depended on local antigen presentation. T helper type-1 (Th1) cells, not Foxp3(+) regulatory T cells, were the chief producers of IL-10 and were not exhausted. Therefore, tracking antigen-specific CD4(+) T cells revealed that IL-10 production by Th1 cells is not due to persistent T-cell antigen receptor stimulation, but rather driven by early antigen encounter at the site of infection. |
DOI | 10.1002/eji.201242715 |
Alternate Journal | Eur. J. Immunol. |
PubMed ID | 23109292 |
Grant List | R01 AI039614 / AI / NIAID NIH HHS / United States R01 AI066016 / AI / NIAID NIH HHS / United States R37 AI027998 / AI / NIAID NIH HHS / United States T32 AI07313 / AI / NIAID NIH HHS / United States T32 CA9138 / CA / NCI NIH HHS / United States |