The Journal of Experimental Medicine
Avanti Polar Lipids
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Published online February 26, 2007
doi:10.1084/jem.20061871
The Journal of Experimental Medicine, Vol. 204, No. 3, 619-631
The Rockefeller University Press, 0022-1007 $30.00
© 2007 Osborne et al.
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ARTICLE

 Impaired CD8 T cell memory and CD4 T cell primary responses in IL-7R{alpha} mutant mice

Lisa C. Osborne1, Salim Dhanji1, Jonathan W. Snow3,4, John J. Priatel1, Melissa C. Ma3, M. Jill Miners1, Hung-Sia Teh1, Mark A. Goldsmith3, and Ninan Abraham1,2

1 Department of Microbiology and Immunology and 2 Department of Zoology, Life Sciences Centre, University of British Columbia Vancouver, British Columbia, Canada V6T 1Z3
3 Gladstone Institute of Virology and Immunology San Francisco, CA 94141
4 Department of Microbiology and Immunology, University of California San Francisco, San Francisco CA 94141

CORRESPONDENCE Ninan Abraham: ninan{at}interchange.ubc.ca

Loss of interleukin (IL)-7 or the IL-7 receptor alpha (IL-7R{alpha}, 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-7R{alpha} Y449XXM motif in mice by knock-in mutagenesis (IL-7R{alpha}449F). Thymic precursors were reduced in number in IL-7R{alpha}449F mice, but in marked contrast to IL-7R{alpha}–/– knockout mice, thymocytes and peripheral T cells developed normally. Strikingly, Listeria infection revealed that CD4 and CD8 T cells had different requirements for IL-7R{alpha} signals. CD4 T cells failed to mount a primary response, but despite normal CD8 primary responses, maintenance of CD8 memory was impaired in IL-7R{alpha}449F mice. Furthermore, we show that Bcl-2 is IL-7R{alpha} Y449 independent and insufficient for IL-7–mediated maintenance of CD8 memory.

Abbreviations used: {gamma}c, gamma common chain; DN, double negative; DP, double positive; ES, embryonic stem; ETP, early thymic progenitor; F, phenylalanine; HP, homeostatic proliferation; HSA, heat stable antigen; HSC, hematopoietic stem cell; LLO, listeriolysin O; PI3, phosphatidylinositol-3; SP, single positive; TSLP, thymic stromal lymphopoietin; Y, tyrosine.


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