Evidence of STAT5-dependent and -independent routes to CD8 memory formation and a preferential role for IL-7 over IL-15 in STAT5 activation.
Interleukin (IL)-7 and IL-15 have non-redundant roles in promoting development of memory CD8(+) T cells. STAT5 is activated by receptors of both cytokines and has also been implicated as a requirement for generation of memory. To determine whether STAT5 activity was required for IL-7 and IL-15-mediated generation of memory, we expressed either wild type (WT) or constitutively active (CA) forms of STAT5a in normal effector cells and then observed their ability to form memory in cytokine replete or deficient hosts. Receptor-independent CA-STAT5a significantly enhanced memory formation in the absence of either cytokine but did not mediate complete rescue. Interestingly, WT-STAT5a expression enhanced memory formation in a strictly IL-7-dependent manner, suggesting that IL-7 is a more potent activator of STAT5 than IL-15 in vivo. These data suggest that the non-redundant requirement for IL-7 and IL-15 is mediated through differential activation of both STAT5-dependent and STAT5-independent pathways.
Kemp
Roslyn A
RA
Division of Immune Cell Biology, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London, UK.
Pearson
Claire F
CF
Cornish
Georgina H
GH
Seddon
Benedict P
BP
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D007156:Immunologic Memory / Q000276:immunology*; D019409:Interleukin-15 / Q000276:immunology*; D015851:Interleukin-7 / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D050505:Mutant Proteins / Q000378:metabolism; D010766:Phosphorylation; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D020395:Receptors, Interleukin-7 / Q000378:metabolism; D012190:Retroviridae / Q000235:genetics; D050799:STAT5 Transcription Factor / Q000276:immunology*; D014161:Transduction, Genetic
D019409:Interleukin-15; D015851:Interleukin-7; D050505:Mutant Proteins; D011948:Receptors, Antigen, T-Cell; D020395:Receptors, Interleukin-7; D050799:STAT5 Transcription Factor; C494093:Stat5a protein, mouse