In vivo depletion of CD4+CD25hi regulatory T cells is associated with improved antiviral responses in cats chronically infected with feline immunodeficiency virus

Mikkelsen, Susan; Reckling, Stacie; Egan, Erin A.; Dean, Gregg A.

doi:10.1016/j.virol.2010.04.016

Cited by 14 publications

(24 citation statements)

References 71 publications

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“…During chronic FIV, SIV or HIV-1 infection it is clear that Treg cells suppress antiviral responses in vitro [10], [12], [13], [14]. We have shown that this suppression is also exerted in vivo during chronic FIV infection [18]. Whether the net effect of suppressing chronic immune activation is beneficial likely depends on the immunologic and virologic set-point of any given individual.…”

Section: Discussionmentioning

confidence: 82%

Partial Regulatory T Cell Depletion Prior to Acute Feline Immunodeficiency Virus Infection Does Not Alter Disease Pathogenesis

et al. 2011

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Feline immunodeficiency virus (FIV) infection in cats follows a disease course similar to HIV-1, including a short acute phase characterized by high viremia, and a prolonged asymptomatic phase characterized by low viremia and generalized immune dysfunction. CD4+CD25hiFoxP3+ immunosuppressive regulatory T (Treg) cells have been implicated as a possible cause of immune dysfunction during FIV and HIV-1 infection, as they are capable of modulating virus-specific and inflammatory immune responses. Additionally, the immunosuppressive capacity of feline Treg cells has been shown to be increased during FIV infection. We have previously shown that transient in vivo Treg cell depletion during asymptomatic FIV infection reveals FIV-specific immune responses suppressed by Treg cells. In this study, we sought to determine the immunological influence of Treg cells during acute FIV infection. We asked whether Treg cell depletion prior to infection with the highly pathogenic molecular clone FIV-C36 in cats could alter FIV pathogenesis. We report here that partial Treg cell depletion prior to FIV infection does not significantly change provirus, viremia, or CD4+ T cell levels in blood and lymphoid tissues during the acute phase of disease. The effects of anti-CD25 mAb treatment are truncated in cats acutely infected with FIV-C36 as compared to chronically infected cats or FIV-naïve cats, as Treg cell levels were heightened in all treatment groups included in the study within two weeks post-FIV infection. Our findings suggest that the influence of Treg cell suppression during FIV pathogenesis is most prominent after Treg cells are activated in the environment of established FIV infection.

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Section: Discussionmentioning

confidence: 82%

Partial Regulatory T Cell Depletion Prior to Acute Feline Immunodeficiency Virus Infection Does Not Alter Disease Pathogenesis

et al. 2011

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“…In fact, when Tregs of FIV-infected cats were depleted in vivo, anti-FIV immune responses were improved. 41 As in cats, Foxp3 þ Tregs in cattle increase in blood after infection with bovine leukemia virus. 80 Similar findings have been shown in other species.…”

Section: Tregs and Infectious Diseasesmentioning

confidence: 99%

Regulatory T Cells and Their Role in Animal Disease

Veiga-Parga

2016

Vet Pathol

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In humans and mouse models, Foxp3 þ regulatory T cells are known to control all aspects of immune responses. However, only limited information exists on these cells' role in diseases of other animals. In this review, we cover the most important features and different types of regulatory T cells, which include those that are thymus-derived and peripherally induced, the mechanisms by which they control immune responses by targeting effector T cells and antigen-presenting cells, and most important, their role in animal health and diseases including cancer, infections, and other conditions such as hypersensitivities and autoimmunity. Although the literature regarding regulatory T cells in domestic animal species is still limited, multiple articles have recently emerged and are discussed. Moreover, we also discuss the evidence suggesting that regulatory T cells might limit the magnitude of effector responses, which can have either a positive or negative result, depending on the context of animal and human disease. In addition, the issue of plasticity is discussed because plasticity in regulatory T cells can result in the loss of their protective function in some microenvironments during disease. Lastly, the manipulation of regulatory T cells is discussed in assessing the possibility of their use as a treatment in the future.

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“…Finally, the ability of the immune system to adequately respond and kill reactivated cells is critical to proposed strategies to purge viral reservoirs. Selective depletion of CD4 + CD25+ cells has been shown to result in improved antiviral responses in cats chronically infected with FIV [83,86], which could potentially be part of a strategy to boost the immune system during or after ALT. There is much still to be learned about these and other interactions between the immune system and latent FIV.…”

Section: Reviewmentioning

confidence: 99%

Feline immunodeficiency virus latency

2013

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Despite highly effective anti-retroviral therapy, HIV is thought to persist in patients within long-lived cellular reservoirs in the form of a transcriptionally inactive (latent) integrated provirus. Lentiviral latency has therefore come to the forefront of the discussion on the possibility of a cure for HIV infection in humans. Animal models of lentiviral latency provide an essential tool to study mechanisms of latency and therapeutic manipulation. Of the three animal models that have been described, the feline immunodeficiency virus (FIV)-infected cat is the most recent and least characterized. However, several aspects of this model make it attractive for latency research, and it may be complementary to other model systems. This article reviews what is known about FIV latency and chronic FIV infection and how it compares with that of other lentiviruses. It thereby offers a framework for the usefulness of this model in future research aimed at lentiviral eradication.

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In vivo depletion of CD4+CD25hi regulatory T cells is associated with improved antiviral responses in cats chronically infected with feline immunodeficiency virus

Cited by 14 publications

References 71 publications

Partial Regulatory T Cell Depletion Prior to Acute Feline Immunodeficiency Virus Infection Does Not Alter Disease Pathogenesis

Partial Regulatory T Cell Depletion Prior to Acute Feline Immunodeficiency Virus Infection Does Not Alter Disease Pathogenesis

Regulatory T Cells and Their Role in Animal Disease

Feline immunodeficiency virus latency

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