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Rapid induction of CD95 ligand and CD4+ T cell-mediated apoptosis by CD137 (4-1BB) costimulation.
Eur J Immunol. 2001 May; 31(5):1410-6.EJ

Abstract

We investigated the cytolytic mechanism by CD4+ T cells in anti-CD3 mAb-induced redirected cytotoxicity against a murine Fc receptor-bearing mastocytoma (P815) transfected with either CD80 or CD137 ligand (CD137L). CD137 costimulation preferentially induced anti-CD3-induced redirected cytotoxicity within 4 h. This cytotoxicity was efficiently abrogated by the addition of anti-CD137L or anti-CD95L mAb, or by treatment with a broad caspase inhibitor, Z-VAD, suggesting that the induced cytotoxicity against CD137L-P815 is dependent on CD95L-mediated apoptosis. In contrast, the cytotoxicity against CD80-P815, but not CD137L-P815 was efficiently inhibited by an inhibitor of perforin-dependent cytotoxicity, concanamycin A. Involvement of CD95L in the CD137L-dependent cytotoxicity was confirmed by a failure of induction of cytotoxicity by CD4+ T cells from CD95L-gene mutated gid mice. A rapid and remarkable induction of CD95L transcription within 1 h was observed by CD137L costimulation. These results demonstrated that CD137L costimulation induces a rapid induction of CD95L on CD4+ T cells and leads to apoptosis of CD95-sensitive target cells. This biological function of CD137 in CD4+ T cells may play an important role for immune homeostasis.

Authors+Show Affiliations

Department of Pathology, National Children's Medical Research Center, Tokyo, Japan.No 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

11465097

Citation

Ebata, T, et al. "Rapid Induction of CD95 Ligand and CD4+ T Cell-mediated Apoptosis By CD137 (4-1BB) Costimulation." European Journal of Immunology, vol. 31, no. 5, 2001, pp. 1410-6.
Ebata T, Mogi S, Hata Y, et al. Rapid induction of CD95 ligand and CD4+ T cell-mediated apoptosis by CD137 (4-1BB) costimulation. Eur J Immunol. 2001;31(5):1410-6.
Ebata, T., Mogi, S., Hata, Y., Fujimoto, J. I., Yagita, H., Okumura, K., & Azuma, M. (2001). Rapid induction of CD95 ligand and CD4+ T cell-mediated apoptosis by CD137 (4-1BB) costimulation. European Journal of Immunology, 31(5), 1410-6.
Ebata T, et al. Rapid Induction of CD95 Ligand and CD4+ T Cell-mediated Apoptosis By CD137 (4-1BB) Costimulation. Eur J Immunol. 2001;31(5):1410-6. PubMed PMID: 11465097.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Rapid induction of CD95 ligand and CD4+ T cell-mediated apoptosis by CD137 (4-1BB) costimulation. AU - Ebata,T, AU - Mogi,S, AU - Hata,Y, AU - Fujimoto,J I, AU - Yagita,H, AU - Okumura,K, AU - Azuma,M, PY - 2001/7/24/pubmed PY - 2001/8/10/medline PY - 2001/7/24/entrez SP - 1410 EP - 6 JF - European journal of immunology JO - Eur. J. Immunol. VL - 31 IS - 5 N2 - We investigated the cytolytic mechanism by CD4+ T cells in anti-CD3 mAb-induced redirected cytotoxicity against a murine Fc receptor-bearing mastocytoma (P815) transfected with either CD80 or CD137 ligand (CD137L). CD137 costimulation preferentially induced anti-CD3-induced redirected cytotoxicity within 4 h. This cytotoxicity was efficiently abrogated by the addition of anti-CD137L or anti-CD95L mAb, or by treatment with a broad caspase inhibitor, Z-VAD, suggesting that the induced cytotoxicity against CD137L-P815 is dependent on CD95L-mediated apoptosis. In contrast, the cytotoxicity against CD80-P815, but not CD137L-P815 was efficiently inhibited by an inhibitor of perforin-dependent cytotoxicity, concanamycin A. Involvement of CD95L in the CD137L-dependent cytotoxicity was confirmed by a failure of induction of cytotoxicity by CD4+ T cells from CD95L-gene mutated gid mice. A rapid and remarkable induction of CD95L transcription within 1 h was observed by CD137L costimulation. These results demonstrated that CD137L costimulation induces a rapid induction of CD95L on CD4+ T cells and leads to apoptosis of CD95-sensitive target cells. This biological function of CD137 in CD4+ T cells may play an important role for immune homeostasis. SN - 0014-2980 UR - https://www.unboundmedicine.com/medline/citation/11465097/Rapid_induction_of_CD95_ligand_and_CD4+_T_cell_mediated_apoptosis_by_CD137__4_1BB__costimulation_ L2 - https://doi.org/10.1002/1521-4141(200105)31:5<1410::AID-IMMU1410>3.0.CO;2-H DB - PRIME DP - Unbound Medicine ER -