Pivotal advance: CTLA-4+ T cells exhibit normal antiviral functions during acute viral infection.
Previous studies have shown that T cells, which are genetically deficient in CTLA-4/CD152 expression, will proliferate uncontrollably, resulting in lethal autoimmune disease. This and other evidence indicate that CTLA-4 plays a critical role in the negative regulation of effector T cell function. In contrast to expectations, BrdU incorporation experiments demonstrated that CTLA-4 expression was associated with normal or even enhanced in vivo proliferation of virus-specific CD4+ and CD8+ T cells following acute lymphocytic choriomeningitis virus or vaccinia virus infection. When compared with CTLA-4- T cells directly ex vivo, CTLA-4+ T cells also exhibited normal antiviral effector functions following stimulation with peptide-coated cells, virus-infected cells, plate-bound anti-CD3/anti-CTLA-4, or the cytokines IL-12 and IL-18. Together, this indicates that CTLA-4 does not directly inhibit antiviral T cell expansion or T cell effector functions, at least not under the normal physiological conditions associated with either of these two acute viral infections.
Raué
Hans-Peter
HP
Vaccine and Gene Therapy Institute, Oregon Health and Science University, 505 N.W. 185th Avenue, Beaverton, OR 97006, USA.
Slifka
Mark K
MK
D000208:Acute Disease; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis*; D000943:Antigens, Differentiation / Q000096:biosynthesis*; D018106:CD28 Antigens / Q000096:biosynthesis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D060908:CTLA-4 Antigen; D049109:Cell Proliferation; D018796:Immunoconjugates / Q000276:immunology*; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D014616:Vaccinia virus / Q000276:immunology*
D015703:Antigens, CD; D000943:Antigens, Differentiation; D018106:CD28 Antigens; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; D018796:Immunoconjugates