DIFFERENTIAL T-CELL COSTIMULATORY REQUIREMENTS IN CD28-DEFICIENT MICE

T cell receptor stimulation without costimulation is insufficient for the induction of an optimal immune response. It is thought that engage ment of the CD28 molecule with its ligand B7 provides an essential cos timulatory signal without which full activation of T cells cannot occu r. A mouse strain with a defective CD28 gene was established. Developm ent of T and B cells in the CD28-deficient mice appeared normal. Howev er, T lymphocytes derived from CD28-/- mutant mice had impaired respon ses to lectins. Lectin stimulation did not trigger interleukin-2 (IL-2 ) production, IL-2 receptor alpha expression was significantly decreas ed, and exogenous IL-2 only partially rescued the CD28 defect. Basal i mmunoglobulin (Ig) concentrations in CD28-deficient mice were about on e-fifth of those found in wild-type controls, with low titers of IgG1 and IgG2b but an increase in IgG2a. In addition, activity of T helper cells in CD28-/- mice was reduced and immunoglobulin class switching w as diminished after infection with vesicular stomatitis virus. However , cytotoxic T cells could still be induced and the mice showed delayed -type hypersensitivity after infection with lymphocytic choriomeningit is virus. Thus, CD28 is not required for all T cell responses in vivo, suggesting that alternative costimulatory pathways may exist.