Non-redundant role for IL-7R signaling for the survival of CD8+ memory T cells.
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-7Ralpha was selectively expressed in the thymus of IL-7Ralpha(-/-) 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.
Carrio
Roberto
R
Department of Microbiology and Immunology, Miller School of Medicine, University of Miami, Miami, FL 33101, USA.
Rolle
Cleo E
CE
Malek
Thomas R
TR
D019264:Adoptive Transfer; D000818:Animals; D002470:Cell Survival / Q000276:immunology; D005434:Flow Cytometry; D006801:Humans; D007156:Immunologic Memory; D019409:Interleukin-15 / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D015851:Interleukin-7 / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D020395:Receptors, Interleukin-7 / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D019409:Interleukin-15; D015851:Interleukin-7; D020395:Receptors, Interleukin-7