Anti-CD2 mAbs suppress cytotoxic lymphocyte activity by the generation of Th2 suppressor cells and receptor blockade.

TitleAnti-CD2 mAbs suppress cytotoxic lymphocyte activity by the generation of Th2 suppressor cells and receptor blockade.
Publication TypeJournal Article
Year of Publication1994
AuthorsChavin KD, Qin L, Yon R, Lin J, Yagita H, Bromberg JS
JournalJ Immunol
Date Published1994 Apr 15
KeywordsAnimals, Antibodies, Monoclonal, Antigens, Differentiation, T-Lymphocyte, CD2 Antigens, CD4-Positive T-Lymphocytes, Cytokines, Cytotoxicity, Immunologic, Dose-Response Relationship, Immunologic, Immunologic Memory, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Receptors, Immunologic, T-Lymphocytes, Cytotoxic, T-Lymphocytes, Helper-Inducer, T-Lymphocytes, Regulatory

The mechanism by which anti-CD2 mAbs inhibit hapten-specific and alloantigen specific CTL was explored. In vivo administration of alpha-CD2 mAbs resulted in 80 to 100% inhibition of alloantigen specific CTLs. Mixing cells from control animals with cells from alpha-CD2-treated groups demonstrated transferable suppression of CTL (40-67% suppression). These suppressor cells were CD4+CD8- and associated with increased IL-4 and TGF-beta in culture as compared with controls. Anti-CD2 mAbs added at the initiation of culture resulted in 60 to 72% inhibition of trinitrophenyl-CTL, whereas mAbs added at the time of assay resulted in less than 50% inhibition of trinitrophenyl-CTLs. F(ab')2 and Fab alpha-CD2 produced inhibition similar to intact mAbs when added at the time of the lytic assay, whereas both produced only modest inhibition in vivo or when added at the initiation of culture. Alloantigen-specific CTLs were not affected by Ab addition to either culture or assay. The immunosuppressive effects were generalizable because a panel of alpha-CD2 mAbs were all comparably effective in suppressing hapten-specific CTLs when administered in vivo. The results demonstrate that the inhibitory effects are the result of blockade of receptor adhesion function during Ag priming or target recognition, Fc-related effects, and the generation of a negative regulatory, CD4+CD8-, IL-4- and TGF-beta-producing TH2 suppressor T cell.

Alternate JournalJ Immunol
PubMed ID7908306
Grant ListAI32655 / AI / NIAID NIH HHS / United States
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Lihui Qin, M.D., Ph.D.

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