TY - JOUR
T1 - Tracking antigen-specific CD4+ T cells throughout the course of chronic Leishmania major infection in resistant mice
AU - Pagán, Antonio J.
AU - Peters, Nathan C.
AU - Debrabant, Alain
AU - Ribeiro-Gomes, Flavia
AU - Pepper, Marion
AU - Karp, Christopher L.
AU - Jenkins, Marc
AU - Sacks, David L.
PY - 2013/2
Y1 - 2013/2
N2 - 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.
AB - 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.
KW - CD4 T cells
KW - IFN-γ
KW - IL-10
KW - Leishmania major
KW - Tetramer
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U2 - 10.1002/eji.201242715
DO - 10.1002/eji.201242715
M3 - Article
C2 - 23109292
AN - SCOPUS:84873748473
SN - 0014-2980
VL - 43
SP - 427
EP - 438
JO - European Journal of Immunology
JF - European Journal of Immunology
IS - 2
ER -