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CD28-independent, TRAF2-dependent costimulation of resting T cells by 4-1BB ligand.
J Exp Med. 1998 Jun 01; 187(11):1849-62.JE

Abstract

4-1BB ligand (4-1BBL) is a member of the tumor necrosis factor (TNF) family expressed on activated antigen-presenting cells. Its receptor, 4-1BB, is a member of the TNF receptor family expressed on activated CD4 and CD8 T cells. We have produced a soluble form of 4-1BBL using the baculovirus expression system. When coimmobilized on plastic with anti-CD3, soluble 4-1BBL induces interleukin (IL)-2 production by resting CD28+ or CD28- T cells, indicating that 4-1BBL can function independently of other cell surface molecules, including CD28, in costimulation of resting T cell activation. At low concentrations of anti-CD3, 4-1BBL is inferior to anti-CD28 in T cell activation. However, when 4-1BB ligand is provided together with strong TCR signals, then 4-1BBL and anti-CD28 are equally potent in stimulation of IL-2 production by resting T cells. We find that TNF receptor-associated factor (TRAF)1 or TRAF2 associate with a glutathione S-transferase-4-1BB cytoplasmic domain fusion protein in vitro. In T cells, we find that association of TRAF1 and TRAF2 with 4-1BB requires 4-1BB cross-linking. In support of a functional role for TRAF2 in 4-1BB signaling, we find that resting T cells isolated from TRAF2-deficient mice or from mice expressing a dominant negative form of TRAF2 fail to augment IL-2 production in response to soluble 4-1BBL. Thus 4-1BB, via the TRAF2 molecule, can provide CD28-independent costimulatory signals to resting T cells.

Authors+Show Affiliations

Department of Immunology, and Amgen Institute, University of Toronto, Toronto, Ontario M5S 1A8, Canada.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

9607925

Citation

Saoulli, K, et al. "CD28-independent, TRAF2-dependent Costimulation of Resting T Cells By 4-1BB Ligand." The Journal of Experimental Medicine, vol. 187, no. 11, 1998, pp. 1849-62.
Saoulli K, Lee SY, Cannons JL, et al. CD28-independent, TRAF2-dependent costimulation of resting T cells by 4-1BB ligand. J Exp Med. 1998;187(11):1849-62.
Saoulli, K., Lee, S. Y., Cannons, J. L., Yeh, W. C., Santana, A., Goldstein, M. D., Bangia, N., DeBenedette, M. A., Mak, T. W., Choi, Y., & Watts, T. H. (1998). CD28-independent, TRAF2-dependent costimulation of resting T cells by 4-1BB ligand. The Journal of Experimental Medicine, 187(11), 1849-62.
Saoulli K, et al. CD28-independent, TRAF2-dependent Costimulation of Resting T Cells By 4-1BB Ligand. J Exp Med. 1998 Jun 1;187(11):1849-62. PubMed PMID: 9607925.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - CD28-independent, TRAF2-dependent costimulation of resting T cells by 4-1BB ligand. AU - Saoulli,K, AU - Lee,S Y, AU - Cannons,J L, AU - Yeh,W C, AU - Santana,A, AU - Goldstein,M D, AU - Bangia,N, AU - DeBenedette,M A, AU - Mak,T W, AU - Choi,Y, AU - Watts,T H, PY - 1998/6/10/pubmed PY - 1998/6/10/medline PY - 1998/6/10/entrez SP - 1849 EP - 62 JF - The Journal of experimental medicine JO - J. Exp. Med. VL - 187 IS - 11 N2 - 4-1BB ligand (4-1BBL) is a member of the tumor necrosis factor (TNF) family expressed on activated antigen-presenting cells. Its receptor, 4-1BB, is a member of the TNF receptor family expressed on activated CD4 and CD8 T cells. We have produced a soluble form of 4-1BBL using the baculovirus expression system. When coimmobilized on plastic with anti-CD3, soluble 4-1BBL induces interleukin (IL)-2 production by resting CD28+ or CD28- T cells, indicating that 4-1BBL can function independently of other cell surface molecules, including CD28, in costimulation of resting T cell activation. At low concentrations of anti-CD3, 4-1BBL is inferior to anti-CD28 in T cell activation. However, when 4-1BB ligand is provided together with strong TCR signals, then 4-1BBL and anti-CD28 are equally potent in stimulation of IL-2 production by resting T cells. We find that TNF receptor-associated factor (TRAF)1 or TRAF2 associate with a glutathione S-transferase-4-1BB cytoplasmic domain fusion protein in vitro. In T cells, we find that association of TRAF1 and TRAF2 with 4-1BB requires 4-1BB cross-linking. In support of a functional role for TRAF2 in 4-1BB signaling, we find that resting T cells isolated from TRAF2-deficient mice or from mice expressing a dominant negative form of TRAF2 fail to augment IL-2 production in response to soluble 4-1BBL. Thus 4-1BB, via the TRAF2 molecule, can provide CD28-independent costimulatory signals to resting T cells. SN - 0022-1007 UR - https://www.unboundmedicine.com/medline/citation/9607925/CD28_independent_TRAF2_dependent_costimulation_of_resting_T_cells_by_4_1BB_ligand_ L2 - https://rupress.org/jem/article-lookup/doi/10.1084/jem.187.11.1849 DB - PRIME DP - Unbound Medicine ER -