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Massive expansion of antigen‐specific CD4 T cells without memory differentiation following acute infection
Author(s) -
Williams Matthew A,
Ravkov Eugene
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.846.13
Subject(s) - lymphocytic choriomeningitis , biology , avidity , adoptive cell transfer , epitope , effector , immunology , cellular differentiation , antigen , cytotoxic t cell , microbiology and biotechnology , t cell , cd8 , immune system , in vitro , genetics , gene
While recent efforts have delineated some of the signals required for CD8 memory T cell differentiation, the signals that lead to the differentiation of CD4 memory T cells are less clear. We analyzed the requirements for CD4 memory differentiation using adoptively transferred CD4 T‐cell receptor transgenic cells (SMARTA) specific for the immunodominant CD4 epitope of lymphocytic choriomeningitis virus (LCMV). Following LCMV infection, effector and memory differentiation of SMARTA cells mimicked the endogenous CD4 response throughout the effector and memory phases. In contrast, infection with a recombinant Listeria expressing the same epitope (Lm‐gp61) resulted in massive initial expansion of SMARTA cells but rapid loss of effector function and failure to form memory. Defective memory differentiation was seen only after stimulation of naive SMARTA cells, was independent of precursor frequency and associated with a gene expression profile indicative of Bim‐mediated apoptosis. Furthermore, their inability to form memory corresponded to a lower functional avidity as compared to endogenous responders in the same host, and long‐lived endogenous CD4+ memory T cells skewed to a higher functional avidity over time. These results support a model in which CD4 memory differentiation and longevity depend on the strength of the antigen‐driven signal during the primary response.