title: Innate immune cell CD45 regulates lymphopenia-induced T cell proliferation.
abstract: The leukocyte-specific tyrosine phosphatase, CD45, severely impacts T cell development and activation by modulating TCR signaling. CD45-deficient (CD45KO) mice have reduced peripheral T cell numbers where CD8 T cells are underrepresented. In this article, we show that CD45KO mice are unable to support efficient homeostatic proliferation, affecting CD8 T cells more than CD4 T cells. Using CD45-RAG1 double-deficient (45RAGKO) mice, we show that lymphopenia-induced proliferation (LIP) of CD45-sufficient T cells is defective in a host environment lacking CD45 on innate immune cells. We identify two deficiencies in the 45RAGKO mice that affect LIP. One involves CD11c(+) cells and the second the production of IL-7 by lymphoid stromal cells. CD45KO dendritic cells were not defective in foreign Ag-induced T cell proliferation, yet CD45KO CD11c(+) cells were unable to rescue the spontaneous LIP in the 45RAGKO mice. This was in contrast with the CD45-sufficient CD11c(+) cells that partially rescued this spontaneous proliferation and did so without affecting IL-7 levels. The absence of CD45 also led to reduced IL-7 production by lymphoid stromal cells, suggesting an indirect effect of CD45 on innate immune cells in influencing IL-7 production by lymphoid stromal cells. These findings demonstrate a novel role for CD45 on innate immune cells in promoting lymphopenia-induced T cell proliferation and suggest that innate immune cells may communicate with stromal cells to regulate IL-7 production.
authors.affiliation: Department of Microbiology and Immunology, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada.
authors.forename: Amy E
authors.initials: AE
authors.lastname: Saunders
authors.affiliation: Department of Microbiology and Immunology, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada.
authors.forename: Yaein A
authors.initials: YA
authors.lastname: Shim
authors.affiliation: Department of Microbiology and Immunology, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada pauline@mail.ubc.ca.
authors.forename: Pauline
authors.initials: P
authors.lastname: Johnson
mesh_terms: D000818:Animals; D039521:CD11c Antigen / Q000096:biosynthesis; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000276:immunology; D007113:Immunity, Innate; D015851:Interleukin-7 / Q000096:biosynthesis; D017493:Leukocyte Common Antigens / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D008231:Lymphopenia / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D017154:Stromal Cells / Q000276:immunology
chemical_list: D039521:CD11c Antigen; D015851:Interleukin-7; D011948:Receptors, Antigen, T-Cell; D017493:Leukocyte Common Antigens; C516770:Ptprc protein, mouse