MAb 18D3 triggering of integrin beta 1 will prevent but not terminate proliferation of human T cells.
Triggering of integrins can deliver signals that will regulate T cell activation and proliferation when coupled with TCR/CD3 signaling. While co-activation stimuli can be achieved either with immobilized natural ligands or immobilized monoclonal antibodies specific for various integrin subunits, counterposing effects can be delivered by ligation of the integrin beta 1 chain (CD29) resulting in the downregulation of T cell proliferation. Thus, integrins may play a pivotal role in cell activation and are involved in both positive and negative regulatory pathways. In this report, anti-beta 1 mAb 18D3 was used to investigate the role of beta 1 in the negative regulation of T cell proliferation. T lymphocytes were stimulated to proliferate when activated with immobilized mAb to CD3 in conjunction with all of a panel of immobilized mAb to different alpha 4 (CD49d) and beta 1 epitopes, except the anti-beta 1.1 mAb 18D3. In soluble form, mAb 18D3 inhibited the induction of DNA synthesis dependent on costimulation of CD3 and the integrin alpha 4 subunit by a mechanism independent of anti-adhesive properties. In kinetic experiments, the addition of mAb 18D3 effectively inhibited the ultimate induction of DNA synthesis at all time points until the time coinciding with the onset of T cell proliferation, indicating that triggering the beta 1.1 epitope may only act to quench activation events prior to cellular commitment to synthesize DNA. MAb 18D3 did not induce cell death nor render cells incompetent for restimulation, but appeared to selectively inhibit IL-2 synthesis with little effect on the induction of IL-2 receptor expression.
Teague
T K
TK
Department of Immunology, University of Texas M. D. Anderson Cancer Center, Houston 77030.
McIntyre
B W
BW
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002448:Cell Adhesion; D002455:Cell Division; D004247:DNA / Q000096:biosynthesis; D006801:Humans; D066298:In Vitro Techniques; D039041:Integrin alpha4beta1; D019012:Integrin beta1; D016023:Integrins / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000502:physiology; D007376:Interleukin-2 / Q000096:biosynthesis / Q000494:pharmacology; D007700:Kinetics; D008213:Lymphocyte Activation; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000502:physiology*
D000911:Antibodies, Monoclonal; D039041:Integrin alpha4beta1; D019012:Integrin beta1; D016023:Integrins; D007376:Interleukin-2; D004247:DNA