CD28 costimulation can promote T cell survival by enhancing the expression of Bcl-XL.
T cell activation through the TCR can result in either cell proliferation or cell death. The role of costimulatory receptors in regulating T cell survival has not been defined. Here, we present data demonstrating that CD28 costimulation enhances the in vitro survival of activated T cells. One mechanism for this enhancement is the ability of CD28 costimulation to augment the production of IL-2, which acts as an extrinsic survival factor for T cells. In addition, CD28 costimulation augments the intrinsic ability of T cells to resist apoptosis. Although CD28 signal transduction had no effect on Bcl-2 expression, CD28 costimulation was found to augment the expression of Bcl-XL substantially. Transfection experiments demonstrated that this level of Bcl-XL could prevent T cell death in response to TCR cross-linking, Fas cross-linking, or IL-2 withdrawal. These data suggest that an important role of CD28 costimulation is to augment T cell survival during antigen activation.
Boise
L H
LH
Gwen Knapp Center for Lupus and Immunology Research, Department of Medicine, University of Chicago, Illinois 60637, USA.
Minn
A J
AJ
Noel
P J
PJ
June
C H
CH
Accavitti
M A
MA
Lindsten
T
T
Thompson
C B
CB
D017209:Apoptosis; D001483:Base Sequence; D018106:CD28 Antigens / Q000378:metabolism*; D002470:Cell Survival; D002478:Cells, Cultured; D006801:Humans; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger / Q000032:analysis; D015290:Second Messenger Systems; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D051020:bcl-X Protein
C494811:BCL2L1 protein, human; D018106:CD28 Antigens; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D051020:bcl-X Protein