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Altered Immune Response in 2B4 Knock‐Out Mice Persistently Infected with LCMV
Author(s) -
Waggoner Stephen N.,
Mathew Porunelloor,
Kumar Vinay,
Welsh Raymond M.
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.858.15
Subject(s) - cd8 , biology , spleen , cytotoxic t cell , immune system , virus , in vivo , immunology , ctl* , t cell , virology , in vitro , biochemistry , microbiology and biotechnology
The signaling lymphocyte activation molecule (SLAM) family receptor, 2B4, has been implicated in regulation of lymphocyte activation in vitro and in vivo. We and others have recently observed that virus‐specific CD8 T cells display sustained, high‐level expression of 2B4 during persistent, but not acute, LCMV infection in mice. Therefore, we hypothesized that 2B4 may play a role in exhaustion of virus‐specific CD8 T cells during chronic virus infection. In contrast to the lymphopenia and T cell clonal exhaustion observed during persistent LCMV infection of wild type mice, persistently infected 2B4‐deficient mice displayed altered liver pathology and marked splenomegaly characterized by increased numbers of all lymphocytes, including CD8 T cells. There were also enhanced numbers of splenic CD8 T cells with a naïve phenotype (CD62L high, CD44 low) and a concomitant increase in the frequency of double‐positive (CD4,CD8) cells within the thymus. Lysis of LCMV peptide‐labeled CTL targets in vivo was markedly reduced in the absence of 2B4, and viral loads were elevated in the spleen and liver. We propose that the absence of 2B4‐induced regulatory signals results in reduced activation of LCMV‐specific CD8 T cells, which poorly control virus replication and resist depletion during viral infection. NIH T32 AI07349‐18