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Role of 4-1BB (CD137) in the functional activation of cord blood CD28(-)CD8(+) T cells.
Blood. 2002 Nov 01; 100(9):3253-60.Blood

Abstract

The CD28(-) subset of CD8(+) T cells is associated with cytotoxic T lymphocyte (CTL) effector function. We investigated a potential role for 4-1BB, a costimulatory molecule structurally related to members of the tumor necrosis factor (TNF) receptor family, in the generation and functional activation of CD28(-) CTLs by using human cord blood (CB) cells composed exclusively of naive CD8(+) T cells with few or no CD28(-) CTLs. The 4-1BB was induced preferentially on the CB CD28(-)CD8(+) T cells when CD28 down-regulation was induced by interleukin 15 (IL-15) and IL-12 stimulation. Anti-4-1BB costimulation induced dramatic phenotypic changes in the CD28(-) CTLs, including restoration of CD28 expression as well as that of memory markers such as CD45RO and CC chemokine receptor 6 (CCR6). Anti-4-1BB costimulation also promoted long-term survival of CD28(-) CTLs, which were sensitive to activation-induced cell death upon anti-CD3 stimulation. The memory-type CD28(+) CTLs induced by anti-4-1BB costimulation acquired a greatly enhanced content of granzyme B, a cytolytic mediator, and enhanced cytotoxic activity as compared with CD28(-) CTLs. Strong cytotoxicity of memory-type CTLs to a 4-1BB ligand-expressing Epstein-Barr virus (EBV)-transformed B-cell line was almost completely abrogated by 4-1BB-Fc, a soluble form of 4-1BB, suggesting involvement of 4-1BB in cytolytic processes. Taken all together, our results suggest that 4-1BB plays a role in the differentiation of effector memory CTLs.

Authors+Show Affiliations

Department of Microbiology and Immunology, Walther Oncology Center, Indiana University School of Medicine, Indianapolis, IN 46202-5254, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

12384425

Citation

Kim, Young-June, et al. "Role of 4-1BB (CD137) in the Functional Activation of Cord Blood CD28(-)CD8(+) T Cells." Blood, vol. 100, no. 9, 2002, pp. 3253-60.
Kim YJ, Brutkiewicz RR, Broxmeyer HE. Role of 4-1BB (CD137) in the functional activation of cord blood CD28(-)CD8(+) T cells. Blood. 2002;100(9):3253-60.
Kim, Y. J., Brutkiewicz, R. R., & Broxmeyer, H. E. (2002). Role of 4-1BB (CD137) in the functional activation of cord blood CD28(-)CD8(+) T cells. Blood, 100(9), 3253-60.
Kim YJ, Brutkiewicz RR, Broxmeyer HE. Role of 4-1BB (CD137) in the Functional Activation of Cord Blood CD28(-)CD8(+) T Cells. Blood. 2002 Nov 1;100(9):3253-60. PubMed PMID: 12384425.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Role of 4-1BB (CD137) in the functional activation of cord blood CD28(-)CD8(+) T cells. AU - Kim,Young-June, AU - Brutkiewicz,Randy R, AU - Broxmeyer,Hal E, PY - 2002/10/18/pubmed PY - 2002/12/11/medline PY - 2002/10/18/entrez SP - 3253 EP - 60 JF - Blood JO - Blood VL - 100 IS - 9 N2 - The CD28(-) subset of CD8(+) T cells is associated with cytotoxic T lymphocyte (CTL) effector function. We investigated a potential role for 4-1BB, a costimulatory molecule structurally related to members of the tumor necrosis factor (TNF) receptor family, in the generation and functional activation of CD28(-) CTLs by using human cord blood (CB) cells composed exclusively of naive CD8(+) T cells with few or no CD28(-) CTLs. The 4-1BB was induced preferentially on the CB CD28(-)CD8(+) T cells when CD28 down-regulation was induced by interleukin 15 (IL-15) and IL-12 stimulation. Anti-4-1BB costimulation induced dramatic phenotypic changes in the CD28(-) CTLs, including restoration of CD28 expression as well as that of memory markers such as CD45RO and CC chemokine receptor 6 (CCR6). Anti-4-1BB costimulation also promoted long-term survival of CD28(-) CTLs, which were sensitive to activation-induced cell death upon anti-CD3 stimulation. The memory-type CD28(+) CTLs induced by anti-4-1BB costimulation acquired a greatly enhanced content of granzyme B, a cytolytic mediator, and enhanced cytotoxic activity as compared with CD28(-) CTLs. Strong cytotoxicity of memory-type CTLs to a 4-1BB ligand-expressing Epstein-Barr virus (EBV)-transformed B-cell line was almost completely abrogated by 4-1BB-Fc, a soluble form of 4-1BB, suggesting involvement of 4-1BB in cytolytic processes. Taken all together, our results suggest that 4-1BB plays a role in the differentiation of effector memory CTLs. SN - 0006-4971 UR - https://www.unboundmedicine.com/medline/citation/12384425/Role_of_4_1BB__CD137__in_the_functional_activation_of_cord_blood_CD28___CD8_+__T_cells_ L2 - https://ashpublications.org/blood/article-lookup/doi/10.1182/blood-2001-11-0136 DB - PRIME DP - Unbound Medicine ER -