The Role of CD4 T Cells in the Pathogenesis of Murine AIDS

Li, Wen; Green, William R.

doi:10.1128/jvi.02711-05

Cited by 22 publications

(42 citation statements)

References 61 publications

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“…To approach the question of which cellular subset(s) is required to express PD-1 to moderate the effects of LP-BM5-induced disease in WT mice, a set of reciprocal adoptive-transfer experiments were undertaken by using highly purified WT, versus PD-1 KO, donor CD4 ϩ T and B cells. Thus, B6.Rag-1 KO recipients were given intravenous parallel transfers of four combinations of purified CD4 ϩ T and B cells, i.e., (i) WT B and CD4 ϩ T cells, (ii) PD-1 KO B and CD4 ϩ T cells, (iii) WT B and PD-1 KO CD4 ϩ T cells, and (iv) PD-1 KO B and WT CD4 ϩ T cells, by using essentially the reconstitution protocol we previously used (23,41,42). Three days later, a portion of the recipients were infected with LP-BM5.…”

Section: Lp-bm5 Retrovirus-infected Pd-1 Ko Mice Demonstrated Greatlymentioning

confidence: 99%

“…To measure serum hyperIg, capture antibodies, affinity-purified goat anti-mouse IgG2a or IgM (Southern Biotechnology Associates, Birmingham, AL), were used to coat 96-well plates after which enzyme-linked immunosorbent assays (ELISAs) were conducted as previously described (21,22,23,41,42). The averages of experimental groups were statistically compared by the Student t test.…”

Section: Lp-bm5 Virus Inoculationsmentioning

confidence: 99%

“…Inoculation of LP-BM5 into B6 mice genetically deficient in or subjected to prior in vivo depletion of either CD4 ϩ T cells or B cells leads to infection but not to virus-induced disease (10,22,23,41,42,66,73). To further characterize the requirement for these lymphoid subsets, we determined that CD154/CD40 interactions are necessary for both the induction and progression of LP-BM5 pathogenesis.…”

mentioning

confidence: 99%

“…Viral load was determined for BM5def and BM5eco as previously described (12,20,24,41,42). Briefly, total RNA was isolated from spleen tissue using TriReagent (Molecular Research Center, Cincinnati, OH) and treated with a DNAfree kit (Ambion, Austin, TX).…”

mentioning

confidence: 99%

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

Green

Okazaki

Honjo

et al. 2008

J Virol

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Section: Lp-bm5 Retrovirus-infected Pd-1 Ko Mice Demonstrated Greatlymentioning

confidence: 99%

Section: Lp-bm5 Virus Inoculationsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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

Green

Okazaki

Honjo

et al. 2008

J Virol

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“…Human immunodeficiency virus type 1/simian immunodeficiency virus induction of PD-1 downregulates T effector cells (14,15), and murine Friend retrovirus infection-induced PD-1 and Tim-3 affect pathogenesis and retroviral loads (16,17), sometimes with "functionless" T cells occurring (14,15). Viral infections can also induce CD4 ϩ FoxP3 ϩ regulatory T (Treg) cells (18), including in LP-BM5 murine retroviral pathogenesis (19)(20)(21). By 5 weeks postinfection (wpi), LP-BM5 causes profound immunodeficiency, with increased susceptibility to "opportunistic" infections and B-cell lymphomas (22,23).…”

Section: Ly6cmentioning

confidence: 99%

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

Green

Wang

Noelle

et al. 2015

J Virol

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Ly6Cϩ/hi and granulocytic/polymorphonuclear-leukocyte-like Ly6G ϩ/hi Ly6C ϩ/Ϫ/lo , use differential suppressive mechanisms to inhibit T cells (12,13). MDSC inhibition of B-cell responses is studied rarely, if at all.Retroviruses are adept at co-opting immunoregulatory mechanisms. Human immunodeficiency virus type 1/simian immunodeficiency virus induction of PD-1 downregulates T effector cells (14,15), and murine Friend retrovirus infection-induced PD-1 and Tim-3 affect pathogenesis and retroviral loads (16, 17), sometimes with "functionless" T cells occurring (14,15). Viral infections can also induce CD4 ϩ FoxP3 ϩ regulatory T (Treg) cells (18), including in LP-BM5 murine retroviral pathogenesis (19-21). 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). This robust direct MDSCinduced inhibition of B-cell responsiveness is novel for murine retrovirus-induced immunosuppression, if not generally. Also, a new negative-checkpoint regulatory ligand, VISTA (V-domain Ig suppressor of T-cell activation) (28-30), also designated PD-1H (31), with homology to PD-L1 has been defined. VISTA can be highly upregulated on myeloid-derived cells and can inhibit T-cell responses in autoimmunity and antitumor immunity in a nonredundant manner with PD-L1 (28).At 5 wpi with LP-BM5, regarding cell surface VISTA expression, the percentage of VISTA ϩ spleen cells had not expanded but VISTA mean fluorescence intensity (MFI) increased and the shape of the positive peak changed, consistent with the dominance of CD4 T-cell-expressed VISTA in uninfected B6 mice (28) and with CD11b ϩ VISTA ϩ cell expansion. Comparison of cells from wild-type (WT), iNOS Ϫ/Ϫ , and VISTA Ϫ/Ϫ B6 mice (32) at 5 wpi confirmed VISTA and CD11b coexpression by the highly enriched monocytic Ly6C ϩ MDSC population we have previously described (10), as depicted in the representative experiment in Fig. 1 (consistent with the average MFI and percent positivity over three experiments [legend to Fig. 1]). Of note, there was minimal contamination with other cells, particularly CD4ϩ Treg cells (legend to Fig. 1). Interestingly, similar monocytic MDSCs could be isolated from the spleens of uninfected mice. These MDSCs expressed levels of VISTA approaching (and, over three repeat experiments, not significantly statistically significantly different from) that of their

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MAIDS resistance-associated gene expression patterns in secondary lymphoid organs

et al. 2008

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Murine acquired immunodeficiency syndrome (MAIDS) is caused by exposure to murine leukemia virus and serves as a model to study human AIDS. In MAIDS-susceptible C57BL/6 mice, virus exposure leads to progressive immune deficiency, while resistant strains such as BALB/c recover from infection and develop protective immunity. The goal of this study was to identify early gene expression patterns that may be important in establishing this strain-specific differential response. Total RNA was isolated from spleens and pooled lymph nodes of both mouse strains at 3 and 7 days post virus infection. The complementary DNA generated from this RNA was hybridized to mouse oligonucleotide DNA microarrays using a strategy that controlled for inherent variability and highlighted only virus-induced changes. Fluorescent intensities were normalized and analyzed for statistically significant differential expression between strains across both time points and lymphoid organs. The majority of the resistance-associated genes was identified at day 3 post-infection and demonstrated the highest fold differences between strains, while more susceptibility-associated sequences were seen at 7 days post-infection. Among the most highly differentially expressed sequences seen at the earlier time point were genes related to protein metabolism, especially serine proteases. Differential patterns of chemokine-related genes were observed at the later time point. The overall pattern of expression suggests strain-specific differences in proteases and chemokines within secondary lymphoid organs shortly after infection influence the likelihood of disease progression.

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The Role of CD4 T Cells in the Pathogenesis of Murine AIDS

Abstract: LP-BM5, a retroviral isolate, induces a disease featuring retrovirus-induced immunodeficiency, designated murine AIDS (MAIDS).

Cited by 22 publications

References 61 publications

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

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

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

MAIDS resistance-associated gene expression patterns in secondary lymphoid organs

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