title: TRAF3 regulates homeostasis of CD8+ central memory T cells.
abstract: Our laboratory reported previously that TNF receptor associated factor 3 (TRAF3) is a positive regulator of TCR signaling and T cell function. In the current study, we present new findings that reveal differential roles for TRAF3 in the regulation of CD4+ and CD8(+) T cells. In response to TCR stimulation in vitro, TRAF3 has greater impact in CD4(+) T cells than in CD8+ T cells. However, T cell-specific TRAF3 deficient mice (CD4Cre TRAF3(fl°x)/(fl°x); T-TRAF3(-/-)) have a greater number of CD4(+)CD44(hi) effector/memory T cells than littermate control (LMC) mice, possibly due to an inefficient suppressive effect of TRAF3 deficient Foxp3+ regulatory T cells. In contrast, CD8(+)CD44(hi)CD62L(hi) central memory (Tcm) cells are markedly reduced in T-TRAF3(-/-) mice in comparison to LMC mice, although CD8(+)CD44(hi)CD62L(l°w) effector memory T (Tem) cells and naïve T cells (CD8(+)CD44(l°w)CD62L(hi)) do not show significant differences in number. Importantly, TRAF3-deficient Tcm cells exhibit defective homeostasis due to impaired IL-15 signaling. These results indicate that the involvement of TRAF3 in IL-15 mediated signaling to T cells plays a previously unappreciated and critical role in CD8(+) Tcm cell regulation and maintenance.
authors.affiliation: Department of Microbiology, University of Iowa, Iowa City, Iowa, United States of America.
authors.forename: Zuoan
authors.initials: Z
authors.lastname: Yi
authors.affiliation: Department of Microbiology, University of Iowa, Iowa City, Iowa, United States of America.
authors.forename: Laura L
authors.initials: LL
authors.lastname: Stunz
authors.affiliation: Department of Microbiology, University of Iowa, Iowa City, Iowa, United States of America; Graduate Immunology Program, University of Iowa, Iowa City, Iowa, United States of America.
authors.forename: Wai Wai
authors.initials: WW
authors.lastname: Lin
authors.affiliation: Department of Microbiology, University of Iowa, Iowa City, Iowa, United States of America; Graduate Immunology Program, University of Iowa, Iowa City, Iowa, United States of America; Department of Internal Medicine, University of Iowa, Iowa City, Iowa, United States of America; VA Medical Center, Iowa City, Iowa, United States of America.
authors.forename: Gail A
authors.initials: GA
authors.lastname: Bishop
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D006706:Homeostasis / Q000276:immunology*; D007156:Immunologic Memory; D019409:Interleukin-15 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008810:Mice, Inbred C57BL; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D015398:Signal Transduction; D048008:TNF Receptor-Associated Factor 3 / Q000172:deficiency / Q000378:metabolism*
chemical_list: D019409:Interleukin-15; D011948:Receptors, Antigen, T-Cell; D048008:TNF Receptor-Associated Factor 3