The Programmed Death-1 and Interleukin-10 Pathways Play a Down-Modulatory Role in LP-BM5 Retrovirus-Induced Murine Immunodeficiency Syndrome

Myeloid-Derived Suppressor Cells in Murine Retrovirus-Induced AIDS Inhibit T- and B-Cell ResponsesIn VitroThat Are Used To Define the Immunodeficiency

“…Because LP-BM5 retrovirus infection-dependent MAIDS features a profound immunodeficiency of both T-cell and B-cell reactivity in susceptible strains of mice, such as prototypic B6 mice (88-93), we considered whether suppressive cells developed during infection. In an attempt to mirror the very strong immunodeficiency associated with LP-BM5-induced MAIDS, we utilized first the very same fundamental and broad immune responses that we and others have established as routine measures of the degree of unresponsiveness of MAIDS: the in vitro proliferative responses to the T-cell mitogen ConA and the B-cell mitogen LPS (61,73,79,81,88). As shown in the representative experiment in Fig.…”

“…However, there is no evidence in support of a direct role for the PD-1-PD-L1 or the IL-10 negative regulatory pathway as an effector phase mechanism of LP-BM5-induced immunodeficiency. Rather, PD-1, PD-L1, and IL-10 knockout mice with the susceptible B6 background all exhibit more, not less, profound pathogenesis after LP-BM5 infection due to a release from normal PD-1-PD-L1 and IL-10 dampening of the pathogenic CD4 ϩ T cells (81). Here, we examine an alternative explanation for the cellular and molecular effectors of LP-BM5 immunodeficiency: the involvement of retrovirus-induced MDSCs.…”

Selective Involvement of the Checkpoint Regulator VISTA in Suppression of B-Cell, but Not T-Cell, Responsiveness by Monocytic Myeloid-Derived Suppressor Cells from Mice Infected with an Immunodeficiency-Causing Retrovirus

“…A CD11b ϩ FcR␥III/II ϩ myeloid cell subset expands during LP-BM5 pathogenesis (26,27). We recently defined these monocytic MDSCs as Gr-1 ϩ Ly6C ϩ/hi Ly6G ϩ/Ϫ/low CD11b ϩ with strong ex vivo inhibition of T-and B-cell responses used to measure LP-BM5-induced immunodeficiency (10).…”

“…ϩ T-effector cell expression of CD154 and ligation of CD40 (22,24,25), and PD-1/PD-L1 and IL-10 downregulate effector T-cell activity (21,26).…”

“…By 5 weeks postinfection (wpi), LP-BM5 causes profound immunodeficiency, with increased susceptibility to "opportunistic" infections and B-cell lymphomas (22, 23). Immunodeficiency requires "pathogenic" CD4ϩ T-effector cell expression of CD154 and ligation of CD40 (22,24,25), and PD-1/PD-L1 and IL-10 downregulate effector T-cell activity (21,26).A CD11b ϩ FcR␥III/II ϩ myeloid cell subset expands during LP-BM5 pathogenesis (26, 27). We recently defined these monocytic MDSCs as Gr-1 ϩ Ly6C ϩ/hi Ly6G ϩ/Ϫ/low CD11b ϩ with strong ex vivo inhibition of T-and B-cell responses used to measure LP-BM5-induced immunodeficiency (10).…”