The role of p53 in regulating antiviral T cell responses.
It is now well established that viral infections can induce large expansions of Ag-specific CD8(+) T cells. These cells divide very rapidly with an estimated doubling time of approximately 6 h. When virus is cleared, the vast majority of these effector CD8 T cells undergo apoptosis. The remaining memory cells persist at constant levels and provide the basis for the accelerated recall response upon rechallenge. The molecular mechanisms that control the rapid proliferation and death of Ag-specific T cells are poorly understood. Because of its important role in controlling cell proliferation and death, we examined antiviral immune responses in p53(-/-) mice using lymphocytic choriomeningitis virus. We found that effector CD8 and CD4 responses were comparable but that memory levels were slightly higher in -/- mice compared with +/+ mice. The lack of a major difference in virus-specific T cell responses between +/+ and -/- mice suggests that p53 only plays a minor role in regulating the proliferation, apoptosis, and maintenance of Ag-specific T cells. Thus, it appears that the primary function of p53 is in controlling "illegitimate" proliferation and tumor development and not in regulating Ag-specific T cell responses.
Grayson
J M
JM
Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA.
Lanier
J G
JG
Altman
J D
JD
Ahmed
R
R
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D007156:Immunologic Memory / Q000235:genetics; D008137:Longitudinal Studies; D008213:Lymphocyte Activation / Q000235:genetics; D018655:Lymphocyte Count; D008216:Lymphocytic Choriomeningitis / Q000235:genetics / Q000276:immunology / Q000821:virology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000821:virology*; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D018984:Epitopes, T-Lymphocyte; D016159:Tumor Suppressor Protein p53