Premium
A distinct role for T‐bet in the maintenance of antigen‐specific CD8 T‐cells during chronic viral infection
Author(s) -
Kao Charlly Chuan,
Intlekofer Andrew M.,
Reiner Steven L.,
Wherry E. John
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.858.10
Subject(s) - cytotoxic t cell , biology , cd8 , lymphocytic choriomeningitis , granzyme b , t cell , immunology , antigen , microbiology and biotechnology , immune system , genetics , in vitro
The T‐box transcription factor, T‐bet, has a well‐established role as a master regulator of CD4 T cell commitment to the T H 1 lineage; however, its importance in the regulation of CD8 differentiation has only recently begun to be elucidated. T‐bet, in cooperation with another highly homologous T‐box family member, eomesodermin, is necessary for induction of the cytokine, interferon‐γ, and the expression of genes integral to the cytolytic machinery, such as granzyme and perforin. Inflammatory stimuli, including IL‐12, can potentiate its expression in cytotoxic T cells after antigenic activation. While T‐bet contributes to the induction of CD8 effector function during acute viral infections, excessive T‐bet expression may impede the ability to differentiate into long‐lived memory cells, instead favoring the formation of short‐lived fully differentiated effector T cells. We studied the expression and function of T‐bet in mice infected with the chronic clone‐13 strain of the lymphocytic choriomeningitis virus (LCMV) and compared the response to that observed with the acute Armstrong strain. Surprisingly, we find that CD8 T cells express lower levels of T‐bet during clone‐13 compared to Armstrong infection even though they are exposed to an environment with persisting antigen and heightened inflammation. This may contribute to the dysfuction (i.e. “exhaustion”) of CD8 T cells observed in chronically infected mice, as T‐bet knockout mice have higher viral burden and lose their antigen‐specific cells within weeks post‐infection. Thus, T‐bet plays a complex role during CD8 differentiation and can have vastly different effects depending on the context of the infection.