IL-2 receptor gamma chain cytokines differentially regulate human CD8+CD127+ and CD8+CD127- T cell division and susceptibility to apoptosis.
Expression of IL-7 receptor alpha (CD127) is associated with naive and memory (i.e. non-effector) CD8+ T cell phenotypes. Effector CD8+ T cells are predominantly CD127- and most die by apoptosis. Therefore, CD127 appears to be a marker for CD8+ T cell differentiation, yet its role in CD8+ T cell survival and memory development is unclear. To address this, we investigated the cell death and cell division of isolated CD8+CD127+ and CD8+CD127- T cells in response to common IL-2 receptor gamma chain (gamma(C)) cytokines other than IL-7. We show here that (i) memory cells (CD127+CD45RA-) divide frequently in response to either IL-2, -4 or -15; (ii) IL-2 and -15 enhance cell division in effector-memory-like cells (CD127-CD45RA+) while IL-4 enhances the cell division of effector cells (CD127-CD45RA-); (iii) CD8+CD127+ T cells are more sensitive to the anti-apoptotic effects of IL-2 or IL-15 than CD8+CD127- T cells and (iv) CD8+CD127+ T cell produce more Bcl-2 in response to IL-2 or IL-15 compared with CD8+CD127- T cells. Therefore, CD8+CD127+ and CD8+CD127- T cells differ in their responsiveness to cell division and anti-apoptotic signals from IL-2, -4 and -15. This suggests a role for gamma(C) cytokines in the pathogenesis of diseases in which CD127 expression is altered on CD8+ T cells such as in progressive viral infections and cancer.
Crawley
Angela M
AM
Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada.
Katz
Tanya
T
Parato
Karl
K
Angel
Jonathan B
JB
D017209:Apoptosis / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002455:Cell Division; D049109:Cell Proliferation; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000276:immunology / Q000378:metabolism; D006801:Humans; D053631:Interleukin Receptor Common gamma Subunit / Q000276:immunology / Q000378:metabolism*; D019409:Interleukin-15 / Q000276:immunology / Q000378:metabolism*; D015847:Interleukin-4 / Q000276:immunology / Q000378:metabolism*; D053699:Interleukin-7 Receptor alpha Subunit / Q000276:immunology / Q000378:metabolism*; D051058:Oncogene Protein v-akt / Q000276:immunology / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000276:immunology / Q000378:metabolism; D050799:STAT5 Transcription Factor / Q000276:immunology / Q000378:metabolism; D019014:fas Receptor / Q000276:immunology / Q000378:metabolism
C499517:FOXO3 protein, human; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; D053631:Interleukin Receptor Common gamma Subunit; D019409:Interleukin-15; D053699:Interleukin-7 Receptor alpha Subunit; D019253:Proto-Oncogene Proteins c-bcl-2; D050799:STAT5 Transcription Factor; D019014:fas Receptor; D015847:Interleukin-4; D051058:Oncogene Protein v-akt