Elevated IL-7 availability does not account for T cell proliferation in moderate lymphopenia.
Lymphopenia-induced proliferation (LIP) is a proliferative program initiated in response to T cell insufficiency caused by acute or chronic immunodepletion. Studies of lymphopenic mice have demonstrated that the cytokine IL-7 and TCR signaling are critical for LIP. We examined how these two factors impact T cell proliferation following transfer into moderately lymphopenic mice. In this study, we show that moderate lymphopenia (∼25% of wild-type lymphocytes) of IL-7Rα knock-in mutant (IL-7Rα(449F)) mice supports T cell proliferation, although with decreased frequency and kinetics compared with cells transferred to severely lymphopenic (5% of wild-type lymphocytes) IL-7Rα(-/-) hosts. Although previous studies have demonstrated that elevated IL-7 levels play an important role in LIP, IL-7 availability was not elevated in IL-7Rα(449F) mice. However, moderate lymphopenia increased access of transferred T cells to self-peptide presented on APCs that can trigger TCR signaling and proliferation. Importantly, we did not detect significant changes in TCR Vβ usage of proliferated T cells recovered from either moderately or severely lymphopenic hosts. Our work demonstrates that polyclonal T cells retain a diverse TCR repertoire following proliferation mediated by either self-peptide-MHC interaction alone or in combination with IL-7, and that T cell reconstitution is most efficient in the presence of increased IL-7 availability.
Department of Microbiology and Immunology, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada.
Lisa Colleen
LC
Osborne
Daniel Timothy
DT
Patton
Jung Hee
JH
Seo
Ninan
N
Abraham
D000818:Animals; D001682:Biological Availability; D049109:Cell Proliferation; D002908:Chronic Disease; D016207:Cytokines / Q000378:metabolism; D055879:Gene Knock-In Techniques; D006801:Humans; D015851:Interleukin-7 / Q000096:biosynthesis* / Q000378:metabolism / Q000502:physiology; D008212:Lymphocyte Depletion; D008231:Lymphopenia / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D008285:Major Histocompatibility Complex / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D020395:Receptors, Interleukin-7 / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics; D013154:Spleen / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology*
D016207:Cytokines; C508605:IL7 protein, human; D015851:Interleukin-7; D020395:Receptors, Interleukin-7; C415350:interleukin-7 receptor, alpha chain