Anti-CD2 monoclonal antibody-induced receptor changes: down modulation of cell surface CD2.

TitleAnti-CD2 monoclonal antibody-induced receptor changes: down modulation of cell surface CD2.
Publication TypeJournal Article
Year of Publication1995
AuthorsLin J, Yon RW, Chavin KD, Qin L, Woodward J, Ding Y, Yagita H, Bromberg JS
Date Published1995 Apr 27
KeywordsAnimals, Antibodies, Monoclonal, Carrier Proteins, CD11 Antigens, CD18 Antigens, CD2 Antigens, CD3 Complex, CD4 Antigens, Cell Membrane, Cytokines, Female, Flow Cytometry, Hyaluronan Receptors, Leukocyte Common Antigens, Lymphocyte Activation, Mice, Mice, Inbred BALB C, Rats, Receptors, Cell Surface, Receptors, Lymphocyte Homing, Spleen, T-Lymphocytes

Anti-CD2 mAbs suppress T cell immunity and prolong allograft survival in vivo while inducing the down-modulation of CD2 expression. Manipulation of cell surface molecules may be important in inducing tolerance, so down-modulation of CD2 expression on T cells by anti-CD2 mAbs was further defined with an in vitro model. The anti-CD2 mAb 12-15 caused CD2 expression on purified splenic T cells to decrease from 83.4 to 22.7% total positive cells while CD3, CD4, and CD8 expression remained unchanged. The expression of other adhesion molecules, LFA-1 alpha (CD11a), LFA-1 beta (CD18), Pgp-1 (CD44), CD45, MEL-14 (L-selectin), and VLA-4 alpha (CD49d), were all increased as a result of anti-CD2 treatment, whereas CD25 (IL-2R), CD48 (CD2 ligand), and ICAM-1 (CD54) remained unchanged. Kinetics showed that CD2 down-modulation was persistent and at the same magnitude from day 1 through day 7 of culture. Anti-CD2 mAb could down modulate CD2 on both CD4 and CD8 splenic lymphocyte subsets, thymocytes, and the T cell lymphoma EL-4; and, non-T cells did not seem to participate in the process of modulation. Mechanistic studies of mAb action showed that, in addition to 12-15, other anti-CD2 mAbs could cause down-modulation of T cell CD2 expression in an epitope and isotype dependent fashion and that CD2 down-modulation correlated with inhibition of receptor-driven T cell stimulation. Intact antibody, including the Fc portion, was required to induce CD2 down-modulation, and additional experiments suggested an interaction with an Fc gamma R other than Fc gamma RII or Fc gamma RIII. CD2 down-modulation did not change with the addition of the cytokines IL-1, IL-2, IL-6, IL-10, TNF alpha, or TGF-beta 1. These results show that anti-CD2 mAbs significantly and persistently down-modulate CD2 on various T cell subpopulations. The mAbs must interact with both the CD2 receptor and an Fc gamma R. CD2 down-modulation is accompanied by changes in the array of other T cell surface receptors that may contribute to mechanisms of anti-CD2-induced immunosuppression.

Alternate JournalTransplantation
PubMed ID7537394
Grant ListAI32655 / AI / NIAID NIH HHS / United States
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