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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

Cytokine-expressing CD8+ T cell levels are lower after anti-CD25 mAb treatment on day 35 post-FIV infection.Popliteal lymph node cells were incubated with monensin for 6 hours prior to quantification of cytokine expressing cells. Percent TNF-α-, IL-2-, and IFN-γ-expressing cells in CD4+ and CD8+ T cell populations were quantified by flow cytometry (n = 8/group). Mean ± SEM is shown. * indicates p<0.05.
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pone-0017183-g006: Cytokine-expressing CD8+ T cell levels are lower after anti-CD25 mAb treatment on day 35 post-FIV infection.Popliteal lymph node cells were incubated with monensin for 6 hours prior to quantification of cytokine expressing cells. Percent TNF-α-, IL-2-, and IFN-γ-expressing cells in CD4+ and CD8+ T cell populations were quantified by flow cytometry (n = 8/group). Mean ± SEM is shown. * indicates p<0.05.

Mentions: Intracellular expression of cytokines TNF-α, IL-2, and IFN-γ was determined in popliteal lymph node CD4+ and CD8+ T cells during acute FIV infection in controland CD25 depleted cats. No significant differences in cytokine expression by T cells were found between the treatment groups at day 14 p.i. (Figure 6). In contrast, CD8+TNF-α+ cell levels were significantly lower in the CD25 depleted group as compared to the vehicle control group at day 35 p.i., and there was a trend of lower IL-2 and IFN-γ expression by CD8+ T cells in the CD25 depleted group as well. Cytokine expression by CD4+ T cells at day 35 p.i. was not significantly different between the groups (Figure 6). By day 54 p.i. no differences were observed in T cell cytokine expression between treatment groups in mesenteric lymph node, retropharyngeal lymph node, and spleen (data not shown).


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)

Cytokine-expressing CD8+ T cell levels are lower after anti-CD25 mAb treatment on day 35 post-FIV infection.Popliteal lymph node cells were incubated with monensin for 6 hours prior to quantification of cytokine expressing cells. Percent TNF-α-, IL-2-, and IFN-γ-expressing cells in CD4+ and CD8+ T cell populations were quantified by flow cytometry (n = 8/group). Mean ± SEM is shown. * indicates p<0.05.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0017183-g006: Cytokine-expressing CD8+ T cell levels are lower after anti-CD25 mAb treatment on day 35 post-FIV infection.Popliteal lymph node cells were incubated with monensin for 6 hours prior to quantification of cytokine expressing cells. Percent TNF-α-, IL-2-, and IFN-γ-expressing cells in CD4+ and CD8+ T cell populations were quantified by flow cytometry (n = 8/group). Mean ± SEM is shown. * indicates p<0.05.
Mentions: Intracellular expression of cytokines TNF-α, IL-2, and IFN-γ was determined in popliteal lymph node CD4+ and CD8+ T cells during acute FIV infection in controland CD25 depleted cats. No significant differences in cytokine expression by T cells were found between the treatment groups at day 14 p.i. (Figure 6). In contrast, CD8+TNF-α+ cell levels were significantly lower in the CD25 depleted group as compared to the vehicle control group at day 35 p.i., and there was a trend of lower IL-2 and IFN-γ expression by CD8+ T cells in the CD25 depleted group as well. Cytokine expression by CD4+ T cells at day 35 p.i. was not significantly different between the groups (Figure 6). By day 54 p.i. no differences were observed in T cell cytokine expression between treatment groups in mesenteric lymph node, retropharyngeal lymph node, and spleen (data not shown).

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