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Non‐redundant role for IL‐7R signaling for the survival of CD8 + memory T cells
Author(s) -
Carrio Roberto,
Rolle Cleo E.,
Malek Thomas R.
Publication year - 2007
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/eji.200737585
Subject(s) - biology , cytotoxic t cell , cd8 , interleukin 15 , ctl* , transgene , microbiology and biotechnology , immunology , memory t cell , t cell , cytokine , immune system , interleukin , in vitro , genetics , gene
Abstract IL‐7 and IL‐15 are important cytokines for CD8 memory T cells. However, the extent that IL‐7 is essential for CD8 T cell memory remains unclear because blocking IL‐7 in vivo results in near complete inhibition of T cell development with the few mature T cells exhibiting functional abnormalities. To bypass this complication, CD8 memory development was examined utilizing a mouse model where transgenic IL‐7Rα was selectively expressed in the thymus of IL‐7Rα –/– mice. T cell development was corrected but the resulting peripheral T cells were essentially IL‐7 non‐responsive. Activation of IL‐7R‐defective OT‐I CD8 + T cells with OVA 257–264 and IL‐2 readily yielded CTL. Upon further culture with IL‐15, these CTL expressed phenotypic and functional properties of central memory‐like cells. Thus, IL‐7R‐defective CD8 + T cells do not exhibit intrinsic defects in effector or memory development. When IL‐7R‐defective OT‐I CTL were adoptively transferred into normal or IL‐15 –/– recipient mice in a non‐inflammatory setting, they converted into memory‐like cells, but did not persist, which was even more striking in IL‐15 –/– recipients. This poor persistence was rescued after expression of transgenic Bcl‐2 in IL‐7R‐defective OT‐I T cells. Collectively, these data indicate that IL‐7 is non‐redundantly required for the survival of CD8 memory T cells.