Expression of Bcl-X-L restores cell survival, but not proliferation and effector differentiation, in CD28-deficient T lymphocytes

Lymphocytes deficient in the T cell costimulatory molecule CD28 exhibit def ects in cell survival, clonal expansion, and differentiation into effector cells. It is known that CD28-mediated signaling results in the upregulation of the Bcl family member Bcl-X-L. To investigate the role that Bcl-X-L pla ys in the various functions of CD28, we expressed Bcl-X-L in CD28-deficient primary T lymphocytes using retrovirus-mediated gene transfer. T cells wer e activated in vitro and infected with Bcl-X-L or control retroviruses; thi s method allows gene expression in activated, cycling cells. Expression of Bcl-X-L in naive T cells was achieved by reconstitution of the immune syste m of lethally irradiated recipient mice with retrovirus-infected purified b one marrow stem cells from CD28(-/-) or wild-type donor mice. Our studies d emonstrate that Bcl-X-L prolongs the survival of CD28(-/-) T cells but does not restore normal proliferation or effector cell development. These resul ts indicate that the various functions of CD28 can be dissociated, and prov ide an experimental approach for testing the roles of downstream signals in the functions of cellular receptors such as CD28.