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Partial regulatory T cell depletion prior to acute feline immunodeficiency virus infection does not alter disease pathogenesis.

Mikkelsen SR, Long JM, Zhang L, Galemore ER, VandeWoude S, Dean GA - PLoS ONE (2011)

Bottom Line: CD4(+)CD25(hi)FoxP3(+) 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.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.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.

View Article: PubMed Central - PubMed

Affiliation: Center for Comparative Medicine and Translational Research, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, United States of America.

ABSTRACT
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(+)CD25(hi)FoxP3(+) 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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FIV proviral load in tissues is unaffected by anti-CD25 mAb treatment.(A–B) Provirus in popliteal lymph nodes was quantified on days 14 and 35 p.i. (C–E) Provirus in mesenteric and retropharyngeal lymph nodes and spleen was quantified on day 54 p.i. * indicates p<0.05.
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pone-0017183-g003: FIV proviral load in tissues is unaffected by anti-CD25 mAb treatment.(A–B) Provirus in popliteal lymph nodes was quantified on days 14 and 35 p.i. (C–E) Provirus in mesenteric and retropharyngeal lymph nodes and spleen was quantified on day 54 p.i. * indicates p<0.05.

Mentions: We found that Treg cell depletion at the onset of FIV infection does not cause significant changes in viremia or proviral load. A trend of higher viremia and peripheral blood mononuclear cell (PBMC) proviral load was found in the CD25 depleted group as compared to the control groups on days 14 and 35 p.i. (Figure 2A and 2B). Proviral load was evaluated at intermediate time points in popliteal lymph nodes sampled on days 14 and 35 p.i.; however, no differences were observed among treatment groups (Figure 3A and 3B). In tissues evaluated terminally at day 54 p.i., proviral load was significantly higher in the mesenteric lymph nodes of CD25 depleted cats as compared to vehicle control cats, but not isotype control cats (Figure 3C). Similarly, proviral load in the retropharyngeal lymph nodes of CD25 depleted cats tended to be higher than in retropharyngeal lymph nodes of control cats (Figure 3D). However, no differences were observed in the spleen (Figure 3E). Both viremia and proviral levels reached set-point by day 54 p.i. in all cats (Figure 2 and 3). Our data indicate that anti-CD25 mAb treatment prior to FIV-C36 infection does not reduce and may in fact slightly augment viral load during acute infection.


Partial regulatory T cell depletion prior to acute feline immunodeficiency virus infection does not alter disease pathogenesis.

Mikkelsen SR, Long JM, Zhang L, Galemore ER, VandeWoude S, Dean GA - PLoS ONE (2011)

FIV proviral load in tissues is unaffected by anti-CD25 mAb treatment.(A–B) Provirus in popliteal lymph nodes was quantified on days 14 and 35 p.i. (C–E) Provirus in mesenteric and retropharyngeal lymph nodes and spleen was quantified on day 54 p.i. * indicates p<0.05.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3045403&req=5

pone-0017183-g003: FIV proviral load in tissues is unaffected by anti-CD25 mAb treatment.(A–B) Provirus in popliteal lymph nodes was quantified on days 14 and 35 p.i. (C–E) Provirus in mesenteric and retropharyngeal lymph nodes and spleen was quantified on day 54 p.i. * indicates p<0.05.
Mentions: We found that Treg cell depletion at the onset of FIV infection does not cause significant changes in viremia or proviral load. A trend of higher viremia and peripheral blood mononuclear cell (PBMC) proviral load was found in the CD25 depleted group as compared to the control groups on days 14 and 35 p.i. (Figure 2A and 2B). Proviral load was evaluated at intermediate time points in popliteal lymph nodes sampled on days 14 and 35 p.i.; however, no differences were observed among treatment groups (Figure 3A and 3B). In tissues evaluated terminally at day 54 p.i., proviral load was significantly higher in the mesenteric lymph nodes of CD25 depleted cats as compared to vehicle control cats, but not isotype control cats (Figure 3C). Similarly, proviral load in the retropharyngeal lymph nodes of CD25 depleted cats tended to be higher than in retropharyngeal lymph nodes of control cats (Figure 3D). However, no differences were observed in the spleen (Figure 3E). Both viremia and proviral levels reached set-point by day 54 p.i. in all cats (Figure 2 and 3). Our data indicate that anti-CD25 mAb treatment prior to FIV-C36 infection does not reduce and may in fact slightly augment viral load during acute infection.

Bottom Line: CD4(+)CD25(hi)FoxP3(+) 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.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.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.

View Article: PubMed Central - PubMed

Affiliation: Center for Comparative Medicine and Translational Research, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, United States of America.

ABSTRACT
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(+)CD25(hi)FoxP3(+) 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.

Show MeSH
Related in: MedlinePlus