Murine AIDS requires CD154/CD40L expression by the CD4 T cells that mediate retrovirus-induced disease: Is CD4 T cell receptor ligation needed?

Li, Wen; Green, William R.

doi:10.1016/j.virol.2006.10.002

Cited by 7 publications

(5 citation statements)

References 59 publications

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“…Splenocyte subpopulation preparation. Splenocyte suspensions were prepared as described previously (39,40). For CD4 and CD8 T cells, cell suspensions from wt or PD-1 Ϫ/Ϫ mice were labeled with anti-CD4 or anti-CD8 paramagnetic beads (MACS; Miltenyi Biotec, Auburn, CA) and positively selected according to the manufacturer's protocol.…”

Section: Methodsmentioning

confidence: 99%

“…Surface staining was performed as described previously (39,40). Spleen cells were incubated with fluorescein isothiocyanate (FITC)-, phycoerythrin (PE)-, or allophycocyanin (APC)-conjugated antibodies, and the resulting direct immunofluorescence was analyzed by a FACSCalibur instrument (BD Bioscience) with Cellquest software (BD Bioscience) to detect the expression of murine CD4 (H129.19), CD8␣ (53-6.7), PD-1 (J43), or FoxP3 (FJK-16S) (BD Pharmingen or eBioscience).…”

Section: Methodsmentioning

confidence: 99%

“…However, the question of their possible epitope specificity versus their polyclonal activation consequent to LP-BM5 infection, which is well described (39), remains unclear.…”

mentioning

confidence: 99%

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Immunotherapy of Murine Retrovirus-Induced Acquired Immunodeficiency by CD4 T Regulatory Cell Depletion and PD-1 Blockade

Green

2011

J Virol

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The LP-BM5 murine retrovirus elicits murine AIDS (MAIDS) (3,32,36,37,42,(46)(47)(48) characterized by an early dysregulated activation of the immune system and an ensuing profound AIDS. Some important features of MAIDS resemble those of human immunodeficiency virus (HIV)/AIDS in humans, including (i) early-onset hypergammaglobulinemia (hyper-Ig); (ii) splenomegaly and lymphadenopathy; (iii) dependence on CD4 T cells for initiation of disease; (iv) loss of CD4 T-cell function and subsequent severely depressed T-and Bcell responses; (v) increased susceptibility to progressive infection and mortality when exposed to normally nonpathogenic microorganisms; and (vi) the development of immunodeficiencyassociated "opportunistic" neoplasms, including end stage B-cell lymphomas (15, 35). While there are also some significant differences between AIDS and MAIDS, the LP-BM5 retroviral system has been widely used as a mouse model for human AIDS (3,32,36,42,[46][47][48].Pathogenic CD4 T effector cells are required for the initiation and progression of MAIDS, and protective CD8 T effector cells are required for MAIDS resistance (28,44,45,54,55,58). CD8 cytolytic T lymphocytes (CTLs) play a critical role in elimination of virus-infected cells and disease control in several retroviral infections, including murine AIDS (in resistant strains) and human HIV-1 infection. Our laboratory has defined the cellular and molecular bases of CD8 CTL-mediated protection in MAIDS-resistant mouse strains (e.g., BALB/c) (28,44,45,54,55,58), as well as insights into the requirement for CD4 T effector cell-mediated initiation/progression of viral pathogenesis in the prototypic MAIDS-susceptible strain, C57BL/6 (B6) (18-23, 39, 40). Thus, interactions between B and CD4 T cells, mediated via the ligation of CD40 and CD40L (CD154), respectively, are essential for LP-BM5-dependent pathogenesis of MAIDS, both for disease induction and for early progression (20)(21)(22). Lack of LP-BM5-induced pathogenesis can be reversed by reconstituting T-cell-lacking B6.nude or B6.TCR␣ Ϫ/Ϫ mice with CD154 ϩ CD4, but not CD154 Ϫ/Ϫ CD4 or wild-type (wt) CD8, T cells (20-22, 39, 40, 67).Using CD40-cytoplasmic-tail TRAF binding site mutant, transgenic, and knockout mice (18) and a panel of CD4 T-cell receptor (TCR) transgenic mice (39), we have gained further insight into the role these pathogenic CD4 Th cells play in mediating LP-BM5 retroviral pathogenesis. However, the question of their possible epitope specificity versus their polyclonal activation consequent to LP-BM5 infection, which is well described (39), remains unclear.In contrast, while a strong protective CD8 T-cell response occurs in MAIDS-resistant strains, such as BALB/c, the lack of comparable LP-BM5-specific CD8 CTLs appears to be crucial to the development of MAIDS in susceptible mouse strains

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Immunotherapy of Murine Retrovirus-Induced Acquired Immunodeficiency by CD4 T Regulatory Cell Depletion and PD-1 Blockade

Green

2011

J Virol

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“…How much the infection of follicular cells contributes to the spread of the virus can only be extrapolated from the data we present here. While it has been shown before that direct, CD40/CD154-dependent interactions of CD4 + T cells and B cells in germinal centers contribute to virus spread and pathogenesis in the mouse LP-BM5 leukemia virus model (32, 33), similar to CD40-dependent interactions of CD4 + T cells and dendritic cells in HIV infection (34), we did not observe an increase in Tfh infection despite the elevated levels of infected follicular B cells in BALB/c mice or in CD8 + T cell-depleted C57BL/6 mice, arguing against direct spread of FV-mWasabi from infected B cells to Tfh cells in the B cell follicle as an important infection-promoting mechanism.…”

Section: Discussionmentioning

confidence: 99%

Infection of B Cell Follicle-Resident Cells by Friend Retrovirus Occurs during Acute Infection and Is Maintained during Viral Persistence

Windmann¹,

Otto²,

Hrycak³

et al. 2019

mBio

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Human immunodeficiency virus is notorious for its ability to avoid clearance by therapeutic interventions, which is partly attributed to the establishment of reservoirs in latently infected cells and cells that reside in immunologically privileged B cell follicles. In the work presented here, we show that cells of the B cell follicle are equally infected by a simple mouse gammaretrovirus. Using fluorescently labeled Friend retrovirus, we found that B cells and T cells in the B cell follicle, while not carrying the bulk of the virus load, were indeed infected by Friend virus in the early acute phase of the infection and persisted in the chronic infection. Our results suggest that infection of follicular cells may be a shared property of lymphotropic viruses and propose the FV infection of mice as a useful model to study strategies for follicular reservoir elimination.

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“…In a number of important ways, the pathogenesis of MAIDS is similar to AIDS. These include: (1) requires pathogenic Th cells to initiate disease and progression; (2) enlarged spleen and lymph nodes; (3) elevated circulating immunoglobulin levels; (4) changes in T cell differentiation; (5) the subsequent loss of functional Th cells and severely depressed T and B cell-mediated immune responses; (6) altered cytokine production, (7) greater susceptibility to infections and mortality from exposure to normally nonpathogenic microbes; (8) susceptibility to opportunistic neoplasms (i.e., B cell lymphoma) [ 43 , 44 , 45 ]; and (9) oxidative stress [ 38 ]. In contrast to HIV-1, infection with LP-BM5 retrovirus targets highly immunosuppressive myeloid suppressor cells [ 36 ], which severely dampen both T and B cell functions, whereas HIV-1 directly infects CD4 Th cells.…”

Section: Maids and Simian Aids (Saids) As Models For Hiv-1mentioning

confidence: 99%

Sympathetic Nerves and Innate Immune System in the Spleen: Implications of Impairment in HIV-1 and Relevant Models

Bellinger

Lorton

2022

Cells

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The immune and sympathetic nervous systems are major targets of human, murine and simian immunodeficiency viruses (HIV-1, MAIDS, and SIV, respectively). The spleen is a major reservoir for these retroviruses, providing a sanctuary for persistent infection of myeloid cells in the white and red pulps. This is despite the fact that circulating HIV-1 levels remain undetectable in infected patients receiving combined antiretroviral therapy. These viruses sequester in immune organs, preventing effective cures. The spleen remains understudied in its role in HIV-1 pathogenesis, despite it hosting a quarter of the body’s lymphocytes and diverse macrophage populations targeted by HIV-1. HIV-1 infection reduces the white pulp, and induces perivascular hyalinization, vascular dysfunction, tissue infarction, and chronic inflammation characterized by activated epithelial-like macrophages. LP-BM5, the retrovirus that induces MAIDS, is a well-established model of AIDS. Immune pathology in MAIDs is similar to SIV and HIV-1 infection. As in SIV and HIV, MAIDS markedly changes splenic architecture, and causes sympathetic dysfunction, contributing to inflammation and immune dysfunction. In MAIDs, SIV, and HIV, the viruses commandeer splenic macrophages for their replication, and shift macrophages to an M2 phenotype. Additionally, in plasmacytoid dendritic cells, HIV-1 blocks sympathetic augmentation of interferon-β (IFN-β) transcription, which promotes viral replication. Here, we review viral–sympathetic interactions in innate immunity and pathophysiology in the spleen in HIV-1 and relevant models. The situation remains that research in this area is still sparse and original hypotheses proposed largely remain unanswered.

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Murine AIDS requires CD154/CD40L expression by the CD4 T cells that mediate retrovirus-induced disease: Is CD4 T cell receptor ligation needed?

Cited by 7 publications

References 59 publications

Immunotherapy of Murine Retrovirus-Induced Acquired Immunodeficiency by CD4 T Regulatory Cell Depletion and PD-1 Blockade

Immunotherapy of Murine Retrovirus-Induced Acquired Immunodeficiency by CD4 T Regulatory Cell Depletion and PD-1 Blockade

Infection of B Cell Follicle-Resident Cells by Friend Retrovirus Occurs during Acute Infection and Is Maintained during Viral Persistence

Sympathetic Nerves and Innate Immune System in the Spleen: Implications of Impairment in HIV-1 and Relevant Models

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