Role of cell cycle regulator E2F1 in regulating CD8 T cell responses during acute and chronic viral infection.
To determine the role of cell cycle regulatory protein E2F1 in T cell immunity, we compared antigen-specific CD8 T cell responses between wild type (+/+) and E2F1-deficient (E2F1-/-) mice following an acute and chronic infection with lymphocytic choriomeningitis virus (LCMV). During an acute LCMV infection, although LCMV-specific effector CD8 T cells from E2F1-/- mice were less susceptible to activation-induced cell death (AICD) in vitro, E2F1 deficiency had no significant effect on the: (1) expansion or contraction of virus-specific CD8 T cell responses; (2) proliferative renewal of memory CD8 T cells in both lymphoid and non-lymphoid organs. Importantly, under conditions of repeated antigenic stimulation in the setting of a chronic LCMV infection, E2F1 deficiency did not preclude the exhaustion of CD8 T cells specific to the immunodominant epitope nucleoprotein 396-404 (NP396-404). Taken together, our studies show that E2F1, an important tumor suppressor and cell cycle regulator, may not have a non-redundant role in regulating CD8 T cell responses in acute and chronic LCMV infections.
Gao
Xiaoyan
X
Department of Pathobiological Sciences, University of Wisconsin-Madison, 2015 Linden Drive, Madison, WI 53706-1102, USA.
Tewari
Kavita
K
Svaren
John
J
Suresh
M
M
D000818:Animals; D017209:Apoptosis; D001117:Arenaviridae Infections / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D018797:Cell Cycle Proteins / Q000235:genetics / Q000502:physiology*; D002455:Cell Division; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D004195:Disease Models, Animal; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D007156:Immunologic Memory; D008217:Lymphocytic choriomeningitis virus; D051379:Mice; D018345:Mice, Knockout; D013045:Species Specificity; D013154:Spleen / Q000276:immunology; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; C493754:E2f1 protein, mouse; D014157:Transcription Factors