Expression of bcl-X(L) restores cell survival, but not proliferation off effector differentiation, in CD28-deficient T lymphocytes.
Lymphocytes deficient in the T cell costimulatory molecule CD28 exhibit defects 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) plays in the various functions of CD28, we expressed Bcl-X(L) in CD28-deficient primary T lymphocytes using retrovirus-mediated gene transfer. T cells were activated in vitro and infected with Bcl-X(L) or control retroviruses; this method allows gene expression in activated, cycling cells. Expression of Bcl-X(L) in naive T cells was achieved by reconstitution of the immune system of lethally irradiated recipient mice with retrovirus-infected purified bone marrow stem cells from CD28(-/)- or wild-type donor mice. Our studies demonstrate that Bcl-X(L) prolongs the survival of CD28(-/)- T cells but does not restore normal proliferation or effector cell development. These results indicate that the various functions of CD28 can be dissociated, and provide an experimental approach for testing the roles of downstream signals in the functions of cellular receptors such as CD28.
Dahl
A M
AM
Immunology Research Division, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
Klein
C
C
Andres
P G
PG
London
C A
CA
Lodge
M P
MP
Mulligan
R C
RC
Abbas
A K
AK
D000818:Animals; D016026:Bone Marrow Transplantation; D018106:CD28 Antigens / Q000276:immunology*; D002454:Cell Differentiation; D002455:Cell Division; D002470:Cell Survival; D018014:Gene Transfer Techniques; D005816:Genetic Complementation Test; D008213:Lymphocyte Activation; D051379:Mice; D008822:Mice, Transgenic; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000276:immunology*; D011828:Radiation Chimera; D012190:Retroviridae; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*; D018418:Th2 Cells; D051020:bcl-X Protein
C494812:Bcl2l1 protein, mouse; D018106:CD28 Antigens; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein