The role of B7 molecules in T cell anergy.
OBJECTIVE
To explore the role and mechanism of B7 molecules in T cell anergy.


METHODS
Anti-B7-1 (CD(80)) and anti-B7-2 (CD(86)) monoclonal antibodies were used to induce T cell anergy. T cell proliferation were assayed by mixed lymphocyte reaction (MLR) with (3)H-TdR incorporation, and cytokine mRNA transcripts were analyzed with reverse transcriptase-polymerase chain reaction (RT-PCR). B7-transfected-CHO cells were used as artificial antigen presentation cells (APCs) in MLR to exclude the effects of other costimulatory molecules.


RESULTS
MLR results showed that the proliferation of T cells was inhibited to various extents by anti-CD(80) or anti-CD(86) monoclonal antibody, the effect of anti-CD(86) antibody was greater than that of anti-CD(80) antibody, and the proliferation was totally blocked when the two were used together. The results of RT-PCR demonstrated that IL-2 and IFN-gamma mRNA transcripts decreased whereas IL-4 mRNA transcripts increased in T cell after treatment with anti-B7 antibo-dies for 24 hours. In MLR with artificial APC, signal one (DR7) alone could stimulate T cell proliferation at a certain threshold intensity. Costimulator B7-1 molecule could help signal one in T cell proliferation. This effect was blocked by anti-CD(80).


CONCLUSIONS
B7 molecules play an important role in T cell immune response. Blockade of B7 family resulted in T cell anergy. The role of CD(86) may be more important than that of CD(80). The conversion of cytokine profile from Th1's to Th2's reflected that anergetic T cells were differentiated into Th2 cells by anti-B7 suggesting that anergetic blockade of costimulator molecules may be one of the mechanisms of T cell.
Wang
Jing
J
Department of Hematology, the Third Hospital, Peking University, Beijing 100083, China.
Ke
Xiaoyan
X
Jia
Liping
L
D000818:Animals; D015703:Antigens, CD / Q000235:genetics; D060887:B7 Antigens; D018122:B7-1 Antigen / Q000378:metabolism; D003412:Cricetulus; D008213:Lymphocyte Activation / Q000276:immunology; D008562:Membrane Glycoproteins; D013601:T-Lymphocytes / Q000276:immunology
D015703:Antigens, CD; D060887:B7 Antigens; D018122:B7-1 Antigen; D008562:Membrane Glycoproteins