Anti-CD2 monoclonal antibody-induced receptor changes: down modulation of cell surface CD2.
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.
Lin
J
J
Department of Microbiology, Medical University of South Carolina, Charleston 29425, USA.
Yon
R W
RW
Chavin
K D
KD
Qin
L
L
Woodward
J
J
Ding
Y
Y
Yagita
H
H
Bromberg
J S
JS
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D018845:CD11 Antigens / Q000096:biosynthesis; D018821:CD18 Antigens / Q000096:biosynthesis; D018801:CD2 Antigens / Q000096:biosynthesis* / Q000276:immunology*; D017252:CD3 Complex / Q000096:biosynthesis; D015704:CD4 Antigens / Q000096:biosynthesis; D002352:Carrier Proteins / Q000096:biosynthesis; D002462:Cell Membrane / Q000276:immunology; D016207:Cytokines / Q000494:pharmacology; D005260:Female; D005434:Flow Cytometry; D018960:Hyaluronan Receptors; D017493:Leukocyte Common Antigens / Q000096:biosynthesis; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D051381:Rats; D011956:Receptors, Cell Surface / Q000096:biosynthesis; D016201:Receptors, Lymphocyte Homing / Q000096:biosynthesis; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
D000911:Antibodies, Monoclonal; D018845:CD11 Antigens; D018821:CD18 Antigens; D018801:CD2 Antigens; D017252:CD3 Complex; D015704:CD4 Antigens; D002352:Carrier Proteins; D016207:Cytokines; D018960:Hyaluronan Receptors; D011956:Receptors, Cell Surface; D016201:Receptors, Lymphocyte Homing; D017493:Leukocyte Common Antigens