T cell-independent interleukin 15Ralpha signals are required for bystander proliferation.
Cytokine driven or "bystander" proliferation of T cells occurs in vivo independently of major histocompatibility complex-T cell receptor interactions. This process may be important for supporting T cell homeostasis and facilitating T cell responses to microbial antigens, and may involve the cytokine interleukin (IL)-15. In this study, we find that IL-15Ralpha-deficient (IL-15Ralpha(-/-)) mice fail to undergo poly I:C or IL-15 driven bystander proliferation of CD8(+) T cells. Surprisingly, IL-15Ralpha(-/-) CD8(+) T cells proliferate in response to poly I:C when adoptively transferred into normal mice, and normal CD8(+) T cells fail to proliferate in IL-15Ralpha(-/-) mice. Normal mice reconstituted with IL-15Ralpha(-/-) bone marrow cells also fail to exhibit bystander responses. Thus, CD8(+) T cell independent IL-15Ralpha signals from radiation sensitive hematopoietic cells are likely required for bystander responses. Moreover, normal CD8(+) T cells proliferate in IL-15Ralpha(-/-) mice after treatment with IL-15. Therefore, IL-15Ralpha signals may mediate a positive feedback loop involving the further physiological production of IL-15. These findings provide new insights into how IL-15Ralpha supports memory phenotype CD8(+) T cell proliferation, and suggest novel mechanisms by which memory CD8(+) T cells are maintained in vivo.
Lodolce
J P
JP
Department of Medicine, University of Chicago, Chicago, IL 60637, USA.
Burkett
P R
PR
Boone
D L
DL
Chien
M
M
Ma
A
A
D019264:Adoptive Transfer; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D002455:Cell Division; D002478:Cells, Cultured; D005260:Female; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000276:immunology / Q000528:radiation effects; D007369:Interferon Inducers / Q000494:pharmacology; D019409:Interleukin-15 / Q000276:immunology / Q000494:pharmacology; D007694:Killer Cells, Natural; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011070:Poly I-C / Q000494:pharmacology; D012333:RNA, Messenger; D011836:Radiation Tolerance; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2 / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*
C508025:Il15ra protein, mouse; D007369:Interferon Inducers; D019409:Interleukin-15; D012333:RNA, Messenger; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2; D011070:Poly I-C