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Cytotoxic T‐lymphocyte antigen 4 blockade augments the T‐cell response primed by attenuated Listeria monocytogenes resulting in more rapid clearance of virulent bacterial challenge
Author(s) -
Rowe Jared H.,
Johanns Tanner M.,
Ertelt James M.,
Lai Joseph C.,
Way Sing Sing
Publication year - 2009
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2008.03001.x
Subject(s) - listeria monocytogenes , cytotoxic t cell , virulence , microbiology and biotechnology , biology , antigen , listeria , immunology , t lymphocyte , blockade , listeria infection , virology , bacteria , in vitro , receptor , biochemistry , genetics , gene
Summary Cytotoxic T‐lymphocyte antigen 4 (CTLA‐4) uniformly suppresses antigen‐specific T cells during chronic infection with bacterial, parasitic or viral pathogens. However, the importance of CTLA‐4 in controlling the T‐cell response during acute infection or after priming with live attenuated vaccine vectors has not been well characterized. Since strategies aimed at blocking CTLA‐4 are being actively developed to therapeutically augment T‐cell‐mediated immunity, the effects of CTLA‐4 blockade on T‐cell activation during these conditions need to be more clearly defined. We have examined the role of CTLA‐4 in a prime‐challenge model of acute bacterial infection using both attenuated and virulent strains of the intracellular bacterium Listeria monocytogenes . Although Foxp3 + CD4 + T cells are the predominant CTLA‐4‐expressing cell type in naïve mice, antigen‐specific Foxp3 − CD4 + cells upregulate CTLA‐4 expression after primary L. monocytogenes infection. Blockade of CTLA‐4 results in increased numbers of L. monocytogenes ‐specific CD4 and CD8 T cells after primary infection with attenuated L. monocytogenes , and confers more rapid bacterial clearance after secondary challenge with virulent L. monocytogenes . Accordingly, CTLA‐4 plays an important suppressive role in T‐cell priming and protective immunity in a prime‐challenge model of acute bacterial infection.