Impaired CD8 T cell memory and CD4 T cell primary responses in IL-7R alpha mutant mice.
Loss of interleukin (IL)-7 or the IL-7 receptor alpha (IL-7Ralpha, CD127) results in severe immunodeficiencies in mice and humans. To more precisely identify signals governing IL-7 function in vivo, we have disrupted the IL-7Ralpha Y449XXM motif in mice by knock-in mutagenesis (IL-7Ralpha(449F)). Thymic precursors were reduced in number in IL-7Ralpha(449F) mice, but in marked contrast to IL-7Ralpha(-/-) knockout mice, thymocytes and peripheral T cells developed normally. Strikingly, Listeria infection revealed that CD4 and CD8 T cells had different requirements for IL-7Ralpha signals. CD4 T cells failed to mount a primary response, but despite normal CD8 primary responses, maintenance of CD8 memory was impaired in IL-7Ralpha(449F) mice. Furthermore, we show that Bcl-2 is IL-7Ralpha Y449 independent and insufficient for IL-7-mediated maintenance of CD8 memory.
Osborne
Lisa C
LC
Department of Microbiology and Immunology, University of British Columbia Vancouver, British Columbia, Canada V6T 1Z3.
Dhanji
Salim
S
Snow
Jonathan W
JW
Priatel
John J
JJ
Ma
Melissa C
MC
Miners
M Jill
MJ
Teh
Hung-Sia
HS
Goldsmith
Mark A
MA
Abraham
Ninan
N
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D002470:Cell Survival / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D007156:Immunologic Memory / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D016297:Mutagenesis, Site-Directed; D020395:Receptors, Interleukin-7 / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics
D020395:Receptors, Interleukin-7; C415350:interleukin-7 receptor, alpha chain