TY - JOUR

T1 - Innate immune cell CD45 regulates lymphopenia-induced T cell proliferation

AU - Saunders, Amy E

AU - Shim, Yaein A

AU - Johnson, Pauline

PY - 2014/9/15

Y1 - 2014/9/15

N2 - 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.

AB - 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.

KW - Animals

KW - CD11c Antigen/biosynthesis

KW - CD4-CD8 Ratio

KW - CD4-Positive T-Lymphocytes/immunology

KW - CD8-Positive T-Lymphocytes/immunology

KW - Cell Differentiation/immunology

KW - Cell Proliferation

KW - Dendritic Cells/immunology

KW - Immunity, Innate

KW - Interleukin-7/biosynthesis

KW - Leukocyte Common Antigens/biosynthesis

KW - Lymphocyte Activation/immunology

KW - Lymphopenia/immunology

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Knockout

KW - Receptors, Antigen, T-Cell/immunology

KW - Signal Transduction/immunology

KW - Stromal Cells/immunology

U2 - 10.4049/jimmunol.1302681

DO - 10.4049/jimmunol.1302681

M3 - Journal article

C2 - 25114101

VL - 193

SP - 2831

EP - 2842

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 6

ER -