Down-regulation of IL-2 receptor alpha (CD25) characterizes human gammadelta-T cells rendered resistant to apoptosis after CD2 engagement in the presence of IL-12.
We recently identified a CD2-mediated, IL-12-dependent signaling pathway that inhibits apoptosis in mitogen-stimulated human gammadelta-T cells. Here we show that gammadelta-T cells which acquire resistance to mitogen-induced apoptosis upregulate IL-12 receptor beta 1 subunit (IL-12Rbeta1); in contrast, gammadelta-T cells which remain sensitive to mitogen-induced apoptosis fail to express IL-12Rbeta1. Next we show that gammadelta-T cells which are rendered resistant to mitogen-induced apoptosis attenuate their expression of the IL-2 receptor alpha chain (IL-2Ralpha/CD25), this in part accounting for their acquired resistance to IL-2-induced death. In contrast, apoptosis-sensitive gammadelta-T cells are shown to persist in their expression of IL-2Ralpha/CD25, thus remaining sensitive to IL-2-induced death. Moreover, we show that apoptosis-resistant, but not apoptosis-sensitive, gammadelta-T cells display an enhanced responsiveness to IL-15, a finding in keeping with the known function of IL-15 as a growth and survival factor. Finally, we present evidence to suggest that this differential responsiveness to IL-15 occurs in part by the increased expression of the IL-15Ralpha chain on apoptosis-resistant gammadelta-T cells, compared to apoptosis-sensitive gammadelta-T cells. The biological and clinical implications of these findings are discussed.
Guo
Ben L
BL
Bone Marrow Transplantation Program, THT-541, University of Alabama at Birmingham, 1900 University Blvd., Birmingham, AL 35294, USA.
Hollmig
Klaus A
KA
Lopez
Richard D
RD
D017209:Apoptosis / Q000187:drug effects / Q000276:immunology*; D018801:CD2 Antigens / Q000276:immunology*; D002478:Cells, Cultured; D015536:Down-Regulation; D005434:Flow Cytometry; D006801:Humans; D018664:Interleukin-12 / Q000276:immunology* / Q000494:pharmacology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology
D018801:CD2 Antigens; D016692:Receptors, Antigen, T-Cell, gamma-delta; D015375:Receptors, Interleukin-2; D018664:Interleukin-12