Crosslinking CD3 with CD2 using sepharose-immobilized antibodies enhances T lymphocyte proliferation

T lymphocyte proliferation can be triggered through interactions with either CD3:Ti, the target of antigen-specific activation, or CD2, the target of an antigen-independent activation pathway. Sepharose-immobilized antibody reactive with CD3 was used to aggregate the T cell receptor complex resulting in T lymphocyte activation. When CD3 was simultaneously crosslinked with CD2 using Sepharose beads coupled to antibodies directed at both determinants, T cell proliferation was markedly enhanced (stimulation index = 8- to 11-fold). A smaller enhancement was induced when CD3 was crosslinked with several other functionally relevant T cell surface molecules. The relative mitogenic potency of the accessory molecules tested was CD2 greater than CD4 greater than CD8 greater than 2H4. Little or no increased proliferation resulted from crosslinking CD3 with class I or class II major histocompatibility antigens. The added proliferation induced by CD3: CD2 crosslinking did not occur in the presence of soluble antibodies directed against CD2. Human thymocytes, the majority of which express both CD3 and CD2, were similarly activated by Sepharose-immobilized antibodies. Our results suggest that specific interactions between T cell surface molecules may play a role in the regulation of lymphocyte activation.