Prolonged exposure of naïve CD8+ T cells to interleukin-7 or interleukin-15 stimulates proliferation without differentiation or loss of telomere length.
Interleukin (IL)-7 and IL-15 are cytokines implicated in homeostatic control of the peripheral CD8 T-cell pool. We compared the effects of IL-7 and IL-15 on survival and proliferation of purified human CD8+ T-cell subsets. Low concentrations of either cytokine reduced the spontaneous apoptosis of all subsets, and enhancement of survival corresponded to the extent of Bcl-2 up-regulation. Surprisingly, although minimal proliferation of naïve CD8+ T cells was observed during the first week of culture with cytokines, a marked expansion of these cells occurred at later time points, particularly in response to IL-15. This occurred largely without phenotypic change or acquisition of effector function, indicating a dissociation of differentiation from proliferation. Notably, progression of naïve CD8+ T cells through several cell divisions resulted in up-regulation of telomerase and the maintenance of telomere length. These data show that IL-7 and IL-15 induce cell proliferation and rescue from apoptosis in a concentration, time and subset-dependent manner, and have implications for the homeostatic expansion of the naïve CD8+ T-cell pool.
Wallace
Diana L
DL
Edward Jenner Institute for Vaccine Research, Compton, UK. di.l.wallace@btinernet.com
Bérard
Marion
M
Soares
Maria V D
MV
Oldham
Janine
J
Cook
Joanne E
JE
Akbar
Arne N
AN
Tough
David F
DF
Beverley
Peter C L
PC
D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D004306:Dose-Response Relationship, Immunologic; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D016130:Immunophenotyping; D019409:Interleukin-15 / Q000276:immunology*; D015851:Interleukin-7 / Q000276:immunology*; D017493:Leukocyte Common Antigens / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology; D019098:Telomerase / Q000378:metabolism; D016615:Telomere / Q000276:immunology*
C515370:CCR7 protein, human; D019409:Interleukin-15; D015851:Interleukin-7; D019253:Proto-Oncogene Proteins c-bcl-2; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; D019098:Telomerase; D017493:Leukocyte Common Antigens