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Role of the stress kinase pathway in signaling via the T cell costimulatory receptor 4-1BB.
J Immunol. 1999 Sep 15; 163(6):2990-8.JI

Abstract

4-1BB is a member of the TNFR superfamily expressed on activated CD4+ and CD8+ T cells. 4-1BB can costimulate IL-2 production by resting primary T cells independently of CD28 ligation. In this study, we report signaling events following 4-1BB receptor aggregation using an Ak-restricted costimulation-dependent T cell hybridoma, C8.A3. Aggregation of 4-1BB on the surface of C8.A3 cells induces TNFR-associated factor 2 recruitment, which in turn recruits and activates apoptosis signal-regulating kinase-1, leading to downstream activation of c-Jun N-terminal/stress-activated protein kinases (JNK/SAPK). 4-1BB ligation also enhances anti-CD3-induced JNK/SAPK activation in primary T cells. Overexpression of a catalytically inactive form of apoptosis signal-regulating kinase-1 in C8.A3 T cells interferes with activation of the SAPK cascade and with IL-2 secretion, consistent with a critical role for JNK/SAPK activation in 4-1BB-dependent IL-2 production. Given the ability of both CD28 and 4-1BB to induce JNK/SAPK activation, we asked whether hyperosmotic shock, another inducer of this cascade, could function to provide a costimulatory signal to T cells. Osmotic shock of resting primary T cells in conjunction with anti-CD3 treatment was found to costimulate IL-2 production by the T cells, consistent with a pivotal role for JNK/SAPK in T cell costimulation.

Authors+Show Affiliations

Department of Immunology, University of Toronto, Ontario, Canada.No 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

10477561

Citation

Cannons, J L., et al. "Role of the Stress Kinase Pathway in Signaling Via the T Cell Costimulatory Receptor 4-1BB." Journal of Immunology (Baltimore, Md. : 1950), vol. 163, no. 6, 1999, pp. 2990-8.
Cannons JL, Hoeflich KP, Woodgett JR, et al. Role of the stress kinase pathway in signaling via the T cell costimulatory receptor 4-1BB. J Immunol. 1999;163(6):2990-8.
Cannons, J. L., Hoeflich, K. P., Woodgett, J. R., & Watts, T. H. (1999). Role of the stress kinase pathway in signaling via the T cell costimulatory receptor 4-1BB. Journal of Immunology (Baltimore, Md. : 1950), 163(6), 2990-8.
Cannons JL, et al. Role of the Stress Kinase Pathway in Signaling Via the T Cell Costimulatory Receptor 4-1BB. J Immunol. 1999 Sep 15;163(6):2990-8. PubMed PMID: 10477561.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Role of the stress kinase pathway in signaling via the T cell costimulatory receptor 4-1BB. AU - Cannons,J L, AU - Hoeflich,K P, AU - Woodgett,J R, AU - Watts,T H, PY - 1999/9/8/pubmed PY - 1999/9/8/medline PY - 1999/9/8/entrez SP - 2990 EP - 8 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J. Immunol. VL - 163 IS - 6 N2 - 4-1BB is a member of the TNFR superfamily expressed on activated CD4+ and CD8+ T cells. 4-1BB can costimulate IL-2 production by resting primary T cells independently of CD28 ligation. In this study, we report signaling events following 4-1BB receptor aggregation using an Ak-restricted costimulation-dependent T cell hybridoma, C8.A3. Aggregation of 4-1BB on the surface of C8.A3 cells induces TNFR-associated factor 2 recruitment, which in turn recruits and activates apoptosis signal-regulating kinase-1, leading to downstream activation of c-Jun N-terminal/stress-activated protein kinases (JNK/SAPK). 4-1BB ligation also enhances anti-CD3-induced JNK/SAPK activation in primary T cells. Overexpression of a catalytically inactive form of apoptosis signal-regulating kinase-1 in C8.A3 T cells interferes with activation of the SAPK cascade and with IL-2 secretion, consistent with a critical role for JNK/SAPK activation in 4-1BB-dependent IL-2 production. Given the ability of both CD28 and 4-1BB to induce JNK/SAPK activation, we asked whether hyperosmotic shock, another inducer of this cascade, could function to provide a costimulatory signal to T cells. Osmotic shock of resting primary T cells in conjunction with anti-CD3 treatment was found to costimulate IL-2 production by the T cells, consistent with a pivotal role for JNK/SAPK in T cell costimulation. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/10477561/Role_of_the_stress_kinase_pathway_in_signaling_via_the_T_cell_costimulatory_receptor_4_1BB_ L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=10477561 DB - PRIME DP - Unbound Medicine ER -