A VLA-4 alpha-chain specific monoclonal antibody enhances CD3-induced IL-2/IL-2 receptor-dependent T-cell proliferation.
Cross-linking the T-cell receptor-associated CD3 complex using the immobilized monoclonal antibody OKT3 can induce low levels of proliferation of purified resting T cells. The effect of coimmobilizing a monoclonal antibody 19H8 specific for the alpha-chain of the integrin VLA-4 on T-cell activation was evaluated. The level of proliferation induced by coimmobilization of the anti-VLA-4 with OKT3 was about 2- to 3-fold over proliferation induced by maximal OKT3 stimulation. The costimulatory activity of 19H8 was dependent on CD3 stimulation since immobilized 19H8 by itself did not induce proliferation. IL-2 secretion was found to be increased over 2-fold with 19H8 costimulation. Addition of exogenous IL-2 resulted in enhanced proliferation of both OKT3 and OKT3 plus 19H8-stimulated cells, but T cells coactivated with 19H8 exhibited a greater capacity to proliferate in response to exogenously supplied IL-2. Analysis of IL-2 receptor expression by flow cytometry revealed that the percentage of CD25-positive cells activated with either OKT3 or OKT3 plus 19H8 is comparable, but the mean fluorescence of cells coactivated with 19H8 is about 3-fold over cells stimulated with OKT3 alone. Dependency of the 19H8 enhanced proliferation on the IL-2/IL-2 receptor system was established by using IL-2-specific neutralizing antisera that reduced the proliferation of T cells activated with OKT3 alone or OKT3 plus 19H8 to comparable levels.2+hese results demonstrate that adhesion molecules may operate at the level of cytokine production and expression of its receptors to modulate the activation state of a cell.
Udagawa
T
T
Department of Immunology, University of Texas M.D. Anderson Cancer Center, Houston 77030.
McIntyre
B W
BW
D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D017252:CD3 Complex / Q000276:immunology; D002455:Cell Division / Q000187:drug effects; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism* / Q000494:pharmacology; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D016029:Receptors, Very Late Antigen / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects*
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D016029:Receptors, Very Late Antigen