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IL-15-dependent induction of 4-1BB promotes antigen-independent CD8 memory T cell survival.
J Immunol. 2006 Mar 01; 176(5):2739-48.JI

Abstract

Mice lacking CD137L (4-1BBL) show normal primary expansion and contraction of the CD8+ T cell response to influenza virus, but exhibit a defect in Ag-specific CD8+ T cell numbers at 3-6 wk postinfection. Previous results showed that the decrease in CD8+ T cell numbers in this model is not due to a programming defect during primary expansion. Thus, it appears that 4-1BB/4-1BBL interactions control the number of surviving CD8+ effector memory cells, late in the primary response. In this report, we asked how 4-1BB on T cells could play a role after Ag has apparently been cleared from the host. We show that IL-15, a cytokine involved in regulation of CD8+ memory T cell survival, induces the expression of 4-1BB on CD8+CD44(high) memory phenotype T cells, but not on CD4+ T cells. The Ag-independent induction of 4-1BB by IL-15 was dependent on MAPK p38 and ERK activation. Transfer of in vitro-generated OT-I CD8+ memory T cells into unimmunized wild-type or 4-1BBL-deficient hosts revealed a 2- to 3-fold survival advantage when 4-1BBL was present, recapitulating the effect seen in the endogenous response to influenza in mice. Decreases in the overall number of memory CD8+ T cells were also observed in the bone marrow of unmanipulated 4-1BBL-deficient mice. These data suggest a model whereby 4-1BB expression on memory CD8+ T cells, perhaps due to encounter with IL-15 in the bone marrow, allows 4-1BB/4-1BBL interactions to maintain memory CD8 T cell survival in the absence of Ag.

Authors+Show Affiliations

Department of Immunology, University of Toronto, Toronto, Ontario, Canada.No affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

16493029

Citation

Pulle, Gayle, et al. "IL-15-dependent Induction of 4-1BB Promotes Antigen-independent CD8 Memory T Cell Survival." Journal of Immunology (Baltimore, Md. : 1950), vol. 176, no. 5, 2006, pp. 2739-48.
Pulle G, Vidric M, Watts TH. IL-15-dependent induction of 4-1BB promotes antigen-independent CD8 memory T cell survival. J Immunol. 2006;176(5):2739-48.
Pulle, G., Vidric, M., & Watts, T. H. (2006). IL-15-dependent induction of 4-1BB promotes antigen-independent CD8 memory T cell survival. Journal of Immunology (Baltimore, Md. : 1950), 176(5), 2739-48.
Pulle G, Vidric M, Watts TH. IL-15-dependent Induction of 4-1BB Promotes Antigen-independent CD8 Memory T Cell Survival. J Immunol. 2006 Mar 1;176(5):2739-48. PubMed PMID: 16493029.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - IL-15-dependent induction of 4-1BB promotes antigen-independent CD8 memory T cell survival. AU - Pulle,Gayle, AU - Vidric,Mariana, AU - Watts,Tania H, PY - 2006/2/24/pubmed PY - 2006/4/29/medline PY - 2006/2/24/entrez SP - 2739 EP - 48 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J. Immunol. VL - 176 IS - 5 N2 - Mice lacking CD137L (4-1BBL) show normal primary expansion and contraction of the CD8+ T cell response to influenza virus, but exhibit a defect in Ag-specific CD8+ T cell numbers at 3-6 wk postinfection. Previous results showed that the decrease in CD8+ T cell numbers in this model is not due to a programming defect during primary expansion. Thus, it appears that 4-1BB/4-1BBL interactions control the number of surviving CD8+ effector memory cells, late in the primary response. In this report, we asked how 4-1BB on T cells could play a role after Ag has apparently been cleared from the host. We show that IL-15, a cytokine involved in regulation of CD8+ memory T cell survival, induces the expression of 4-1BB on CD8+CD44(high) memory phenotype T cells, but not on CD4+ T cells. The Ag-independent induction of 4-1BB by IL-15 was dependent on MAPK p38 and ERK activation. Transfer of in vitro-generated OT-I CD8+ memory T cells into unimmunized wild-type or 4-1BBL-deficient hosts revealed a 2- to 3-fold survival advantage when 4-1BBL was present, recapitulating the effect seen in the endogenous response to influenza in mice. Decreases in the overall number of memory CD8+ T cells were also observed in the bone marrow of unmanipulated 4-1BBL-deficient mice. These data suggest a model whereby 4-1BB expression on memory CD8+ T cells, perhaps due to encounter with IL-15 in the bone marrow, allows 4-1BB/4-1BBL interactions to maintain memory CD8 T cell survival in the absence of Ag. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/16493029/IL_15_dependent_induction_of_4_1BB_promotes_antigen_independent_CD8_memory_T_cell_survival_ L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=16493029 DB - PRIME DP - Unbound Medicine ER -