CD8 T cell responses to lymphocytic choriomeningitis virus in early growth response gene 1-deficient mice.
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 CD8alpha(+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.
Singh
Anju
A
Department of Pathobiological Sciences, University of Wisconsin, Madison, WI 53706, USA.
Svaren
John
J
Grayson
Jason
J
Suresh
M
M
D000208:Acute Disease; D019264:Adoptive Transfer; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation / Q000821:virology*; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured / Q000166:cytology; D004268:DNA-Binding Proteins / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D051766:Early Growth Response Protein 1; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D017874:Immediate-Early Proteins / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D018655:Lymphocyte Count; D008216:Lymphocytic Choriomeningitis / Q000235:genetics / Q000276:immunology / Q000473:pathology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D008264:Macrophages / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D014157:Transcription Factors / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology
D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; D018984:Epitopes, T-Lymphocyte; D017874:Immediate-Early Proteins; D014157:Transcription Factors