Title | CD3 and CD2 ligation alters CD49d epitope expression. |
Publication Type | Journal Article |
Year of Publication | 1995 |
Authors | Lin J, Qin L, Chavin KD, Ding Y, Punch JD, Yang Q, Burkly LC, Bromberg JS |
Journal | Pathobiology |
Volume | 63 |
Issue | 3 |
Pagination | 119-32 |
Date Published | 1995 |
ISSN | 1015-2008 |
Keywords | Animals, Antibodies, Monoclonal, Antigens, CD, CD2 Antigens, CD3 Complex, Cell Adhesion Molecules, Epitopes, Female, Graft Rejection, Heart Transplantation, Integrin alpha4, Integrins, Ligands, Lymphocyte Activation, Mice, Mice, Inbred BALB C, Protein Binding, T-Lymphocytes |
Abstract | The combination of anti-CD2 plus anti-CD3 monoclonal antibodies (mAbs) synergistically prolongs allograft survival and induces antigen-specific tolerance. Since altered expression of cell surface molecules might be important for tolerance induction, the effect of anti-CD2 and anti-CD3 mAbs on the expression of adhesion molecules was analyzed on splenic T cells with an in vitro model. The anti-CD2 mAb, 12-15, alone had no effect on the expression of integrin alpha 4-chain epitopes recognized by two anti-CD49d (VLA-4 alpha) mAbs, R1-2 and PS/2. The anti-CD3 mAb, 2C11, caused R1-2 epitope expression to decrease, while PS/2 epitope expression remained unchanged. The combination of anti-CD2 and anti-CD3 mAbs further decreased R1-2 epitope expression while preserving PS/2 epitope expression. The expression of integrin beta 1 and beta 7 chains, each of which form heterodimers with alpha 4 chains, also remained unchanged. Expression of other integrin, selectin, or immunoglobulin superfamily molecules (CD11a, CD18, CD44, CD45, CD48, CD54 and CD62L) were all significantly increased by anti-CD2 or anti-CD3 mAbs. Decreased R1-2 epitope expression was anti-CD3 dependent and specifically augmented by anti-CD2 mAb. CD2-regulated decreases in R1-2 epitope expression correlated with increased cAMP and could be prevented by addition of high doses of IL-2 but was not affected by the addition of other cytokines. R1-2 alpha 4 epitope expression could be specifically restored by the divalent cation Mn2+, which also increased functional binding to the VCAM-1 ligand. Significantly, the R1-2 but not the PS/2 mAb prolonged graft survival in a cardiac allograft model. These results show that anti-CD2 and anti-CD3 mAbs selectively decrease integrin alpha 4 chain epitope expression on T cells through conformational regulation. Decreased expression of a CD49d epitope is unique in comparison to the up-modulation of other T-cell adhesion receptors. These changes correlate with functional effects and provide an additional mechanistic explanation for the synergistic effect of anti-CD2 plus anti-CD3 in producing tolerance. |
DOI | 10.1159/000163943 |
Alternate Journal | Pathobiology |
PubMed ID | 8821628 |
Related Faculty:
Lihui Qin, M.D., Ph.D.