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 antivral 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.