Anti-T12, an anti-CD6 monoclonal antibody, can activate human T lymphocytes.
Anti-T12 is a murine IgM mAb that recognizes the 130-kDa CD6 glycoprotein on mature human T lymphocytes. Examination of the in vitro effects of this mAb on freshly isolated T cells demonstrates that anti-T12 can induce T cell activation. Such activation is macrophage-dependent, and optimal stimulation occurs with 0.2 to 5 micrograms/ml of purified mAb. This response to soluble mAb is detectable at day 4 to 5 of culture, and peak [3H]TdR uptake is observed at day 7. In a highly similar fashion, the mAb causes a marked augmentation of the autologous mixed lymphocyte reaction, without altering the kinetics of that response. Although optimal anti-CD3 mAb induced mitogenesis is unaffected by anti-T12, suboptimal stimulation of macrophage-depleted T cells by small amounts of immobilized anti-CD3 can be dramatically enhanced when anti-CD3 and anti-T12 are cross-linked together. A soluble nonmitogenic anti-CD3 mAb completely inhibits anti-T12-mediated T cell activation. IL-2R expression is induced by anti-T12 stimulation in 10 to 30% of T cells, and T cell proliferation is substantially inhibited by anti-IL-2R mAb, indicating that anti-T12 induced T cell activation and proliferation utilizes an IL-2-dependent pathway. Isolated CD4+ but not CD8+ cells are stimulated to proliferate, but the CD8+ cells in unseparated T cell preparations activated by anti-T12 do proliferate comparably to the CD4+ cells in such cultures. These data indicate that relatively weak activation of T cells via the TCR/CD3 complex may be augmented significantly by CD6-mediated signals induced by the anti-T12 mAb. The findings suggest that the CD6 T cell membrane protein may have the capacity to function as a physiologically important structure involved in the regulation of T cell activation.
Gangemi
R M
RM
Department of Medicine, New England Medical Center Hospitals, Boston, MA.
Swack
J A
JA
Gaviria
D M
DM
Romain
P L
PL
D000276:Adjuvants, Immunologic / Q000502:physiology; D000328:Adult; D000911:Antibodies, Monoclonal / Q000502:physiology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D002448:Cell Adhesion; D002478:Cells, Cultured; D006801:Humans; D007376:Interleukin-2 / Q000502:physiology; D008213:Lymphocyte Activation; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology; D010641:Phenotype; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology* / Q000502:physiology
D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell