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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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Related in: MedlinePlus

FIV-specific IFN-γ responses during acute infection are not altered by anti-CD25 mAb treatment.Popliteal lymph node cells from day 14 and 35 p.i. and mesenteric and retropharyngeal lymph node cells and spleen cells from day 54 p.i. were incubated for 48 hours with 100 µg/mL FIV p24 peptides or 1% DMSO/media as a background control. IFN-γ spot forming cells (SFCs) per million cells from CD25 depleted, isotype control, and vehicle control treated groups in response to FIV p24 minus background were determined by ELISpot (n = 8/group).
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pone-0017183-g007: FIV-specific IFN-γ responses during acute infection are not altered by anti-CD25 mAb treatment.Popliteal lymph node cells from day 14 and 35 p.i. and mesenteric and retropharyngeal lymph node cells and spleen cells from day 54 p.i. were incubated for 48 hours with 100 µg/mL FIV p24 peptides or 1% DMSO/media as a background control. IFN-γ spot forming cells (SFCs) per million cells from CD25 depleted, isotype control, and vehicle control treated groups in response to FIV p24 minus background were determined by ELISpot (n = 8/group).

Mentions: We have previously shown that in vivo Treg cell depletion in cats chronically infected with FIV unmasks existing FIV-specific IFN-γ secreting cells [18]. We asked whether CD25 depletion before FIV infection would allow a more robust induction of FIV-specific immune responses. Lymphocytes were stimulated with FIV p24 peptides in an IFN-γ ELISpot assay. No significant differences were found between the groups; however, there was a trend of fewer FIV-specific IFN-γ secreting cells in the CD25 depleted group as compared to the control groups in tissues analyzed from days 14, 35, and 54 p.i. (Figure 7).


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-specific IFN-γ responses during acute infection are not altered by anti-CD25 mAb treatment.Popliteal lymph node cells from day 14 and 35 p.i. and mesenteric and retropharyngeal lymph node cells and spleen cells from day 54 p.i. were incubated for 48 hours with 100 µg/mL FIV p24 peptides or 1% DMSO/media as a background control. IFN-γ spot forming cells (SFCs) per million cells from CD25 depleted, isotype control, and vehicle control treated groups in response to FIV p24 minus background were determined by ELISpot (n = 8/group).
© Copyright Policy
Related In: Results  -  Collection

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

pone-0017183-g007: FIV-specific IFN-γ responses during acute infection are not altered by anti-CD25 mAb treatment.Popliteal lymph node cells from day 14 and 35 p.i. and mesenteric and retropharyngeal lymph node cells and spleen cells from day 54 p.i. were incubated for 48 hours with 100 µg/mL FIV p24 peptides or 1% DMSO/media as a background control. IFN-γ spot forming cells (SFCs) per million cells from CD25 depleted, isotype control, and vehicle control treated groups in response to FIV p24 minus background were determined by ELISpot (n = 8/group).
Mentions: We have previously shown that in vivo Treg cell depletion in cats chronically infected with FIV unmasks existing FIV-specific IFN-γ secreting cells [18]. We asked whether CD25 depletion before FIV infection would allow a more robust induction of FIV-specific immune responses. Lymphocytes were stimulated with FIV p24 peptides in an IFN-γ ELISpot assay. No significant differences were found between the groups; however, there was a trend of fewer FIV-specific IFN-γ secreting cells in the CD25 depleted group as compared to the control groups in tissues analyzed from days 14, 35, and 54 p.i. (Figure 7).

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