Limits...
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.

Show MeSH

Related in: MedlinePlus

Anti-FIV p24, but not anti-FIV gp95, IgG titers are significantly lower after anti-CD25 mAb treatment during acute FIV infection.(A) Anti-FIV gp95 and (B) anti-FIV p24 IgG titers were quantified in serum samples on days 0, 7, 14, 35, and 54 post-FIV infection. Positive antibody titers were calculated based on a 3-fold higher optical density than day 0 pre-inoculation controls. Mean ± SEM is shown. Statistical significance was determined between treatment groups for each time point (n = 8/group). * indicates p<0.05.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3045403&req=5

pone-0017183-g008: Anti-FIV p24, but not anti-FIV gp95, IgG titers are significantly lower after anti-CD25 mAb treatment during acute FIV infection.(A) Anti-FIV gp95 and (B) anti-FIV p24 IgG titers were quantified in serum samples on days 0, 7, 14, 35, and 54 post-FIV infection. Positive antibody titers were calculated based on a 3-fold higher optical density than day 0 pre-inoculation controls. Mean ± SEM is shown. Statistical significance was determined between treatment groups for each time point (n = 8/group). * indicates p<0.05.

Mentions: Neutralizing antibodies have been shown to play a role in controlling FIV replication. Anti-FIV gp95 IgG titers were not significantly different between the groups during acute FIV infection (Figure 8A); however, anti-FIV p24 IgG titers were significantly higher in the vehicle control group as compared to the CD25 depleted group on days 7 and 14 p.i. (Figure 8B). These data may explain why viral load was slightly higher in the CD25 depleted group at certain time points 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)

Anti-FIV p24, but not anti-FIV gp95, IgG titers are significantly lower after anti-CD25 mAb treatment during acute FIV infection.(A) Anti-FIV gp95 and (B) anti-FIV p24 IgG titers were quantified in serum samples on days 0, 7, 14, 35, and 54 post-FIV infection. Positive antibody titers were calculated based on a 3-fold higher optical density than day 0 pre-inoculation controls. Mean ± SEM is shown. Statistical significance was determined between treatment groups for each time point (n = 8/group). * indicates p<0.05.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0017183-g008: Anti-FIV p24, but not anti-FIV gp95, IgG titers are significantly lower after anti-CD25 mAb treatment during acute FIV infection.(A) Anti-FIV gp95 and (B) anti-FIV p24 IgG titers were quantified in serum samples on days 0, 7, 14, 35, and 54 post-FIV infection. Positive antibody titers were calculated based on a 3-fold higher optical density than day 0 pre-inoculation controls. Mean ± SEM is shown. Statistical significance was determined between treatment groups for each time point (n = 8/group). * indicates p<0.05.
Mentions: Neutralizing antibodies have been shown to play a role in controlling FIV replication. Anti-FIV gp95 IgG titers were not significantly different between the groups during acute FIV infection (Figure 8A); however, anti-FIV p24 IgG titers were significantly higher in the vehicle control group as compared to the CD25 depleted group on days 7 and 14 p.i. (Figure 8B). These data may explain why viral load was slightly higher in the CD25 depleted group at certain time points 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