Alpha 4 beta 1 (CD49d/CD29) integrin costimulation of human T cells enhances transcription factor and cytokine induction in the absence of altered sensitivity to anti-CD3 stimulation

Author & Article Information Authors: T Udagawa; D G Woodside; B W McIntyre Online ISSN: 1550-6606 Print ISSN: 0022-1767 Copyright © 1996 by American Association of Immunologists Source | J Immunol (1996) 157 (5): 1965–1972. https://doi.org/10.4049/jimmunol.157.5.1965 Abstract The integrin alpha 4 beta 1 can provide a costimulus to induce IL-2 secretion and IL-2R expression leading to enhanced proliferation of purified, peripheral blood T cells. Similar to expression of IL-2, we demonstrated that recombinant vascular-cell adhesion molecule-1, when co-immobilized with anti-CD3 mAb, significantly enhanced the induction of transcription factors NF-AT, AP-1, and NF-kappa B as determined by electromobility shift assays. alpha 4 beta 1 ligation alone had no effect on transcription factor binding. The requirements for induction of transcription factors reflected the requirements for the secretion of multiple cytokines, including IL-2, TNF-alpha, IFN-gamma, and granulocyte macrophage-CSF. In contrast to freshly isolated T cells, in vitro-cultured T cells did not require costimulation for cytokine secretion in response to anti-CD3 alone. Comparison of the dose response to anti-CD3 stimulation demonstrated that half-maximal induction of IL-2 was achieved using the same dose of anti-CD3 for both freshly isolated and cultured T cells. Furthermore, the dose of OKT3 required to achieve half-maximal activation was the same using PMA or different concentrations of alpha 4 beta 1 ligands. Therefore, costimulation by alpha 4 beta 1 ligands was not due to stabilization of the interaction of the cells with its substrate. We conclude, rather, that alpha 4 beta 1 in freshly isolated T cells delivers a distinct signal that synergizes early with signals initiated by TCR/CD3 ligation to induce DNA binding of multiple transcription factors required for cytokine gene induction. Read Article See the original article here | The Journal of Immunology Alpha 4 Beta 1 Integrin T Cell Costimulation Cytokine Induction in T Cells NF-AT and NF-kappa B Activation Immune Cell Signaling Rob Bent Previous Previous Regulation of human T lymphocyte coactivation with an alpha4 integrin antagonist peptide Next Next Endothelial intercellular adhesion molecule-1 expression is suppressed in human malignancies: the role of angiogenic factors 2450 Holcombe Blvd, Suite J Houston, TX 77021 [email protected] © 2025. 7 Hills Pharma Inc. Menu Home About Leadership Technology News & Publications Contact Newsletter Block This newsletter signup form needs a storage option. Edit the block and enter a storage location via the Storage tab. Subscribe Sign up with your email address to receive news and updates. Email Address Sign Up We respect your privacy. Thank you!

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