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The Journal of Immunology, 2004, 173: 3855-3862.
Copyright © 2004 by The American Association of Immunologists

CD8 T Cell Responses to Lymphocytic Choriomeningitis Virus in Early Growth Response Gene 1-Deficient Mice1

Anju Singh*, John Svaren{dagger}, Jason Grayson{ddagger} and M. Suresh2,*

Departments of * Pathobiological Sciences and {dagger} Comparative Biosciences, University of Wisconsin, Madison, WI 53706; and {ddagger} Department of Microbiology and Immunology, Wake Forest University School of Medicine, Winston-Salem, NC 27157

Previous in vitro work has implicated a role for transcriptional factor early growth response gene 1 (EGR1) in regulating immune responses. However, the in vivo role of EGR1 in orchestrating T cell responses has not been studied. To investigate the importance of EGR1 in T cell immunity, we compared Ag-specific CD8 T cell responses between wild type (+/+) and EGR1-deficient (EGR1–/–) mice following an acute infection with lymphocytic choriomeningitis virus (LCMV). These studies revealed that the expansion of LCMV-specific CD8 T cells was substantially reduced in EGR1–/– mice, as compared with +/+ mice. The reduced numbers of LCMV-specific CD8 T cells in EGR1–/– mice were not due to an intrinsic T cell defect per se because purified EGR1-deficient T cells exhibited normal proliferative response to anti-CD3 stimulation in vitro, and underwent normal activation and expansion in response to LCMV upon adoptive transfer into T cell-deficient mice. Furthermore, adoptive transfer of CD8 T cells bearing a transgenic TCR into EGR1–/– mice showed that EGR1 deficiency in non-CD8 T cells impaired CD8 T cell expansion in vivo following an LCMV infection. Further investigations on accessory cells showed that bone marrow-derived dendritic cells from EGR1–/– mice did not exhibit detectable impairment to prime Ag-specific CD8 T cell responses in vivo. However, in LCMV-infected mice, EGR1 deficiency selectively impaired the maturation of CD8{alpha}+ve plasmacytoid dendritic cells. Taken together, our findings suggest that EGR1 might promote expansion of CD8 T cells during an acute viral infection by modulating the cues in the lymphoid microenvironment.




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