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Comparative Study
. 2009 Jan;155(1):35-43.
doi: 10.1111/j.1365-2249.2008.03797.x.

Level, phenotype and activation status of CD4+FoxP3+ regulatory T cells in patients chronically infected with human immunodeficiency virus and/or hepatitis C virus

N I Rallón  1 , M López, V Soriano, J García-Samaniego, M Romero, P Labarga, P García-Gasco, J González-Lahoz, J M Benito
Affiliations
Comparative Study

Level, phenotype and activation status of CD4+FoxP3+ regulatory T cells in patients chronically infected with human immunodeficiency virus and/or hepatitis C virus

N I Rallón et al. Clin Exp Immunol. 2009 Jan.

Abstract

CD4(+) regulatory T (T(reg)) cells have been involved in impaired immunity and persistence of viral infections. Herein, we report the level, phenotype and activation status of T(reg) cells in patients chronically infected with human immunodeficiency virus (HIV) and/or hepatitis C virus (HCV). Expression of CD25, CD45RA, CD27, CD127 and CD38 was assessed on these cells using polychromatic flow cytometry in 20 healthy controls, 20 HIV-monoinfected, 20 HCV-monoinfected and 31 HIV/HCV-co-infected patients. T(reg) cells were defined as CD4(+)forkhead box P3 (FoxP3)(+). The percentage of T(reg) cells was increased significantly in HIV patients compared with controls. Moreover, there was a significant inverse correlation between CD4 counts and T(reg) cell levels. Fewer than 50% of T(reg) cells expressed CD25, with differences in terms of CD127 expression between CD25(+) and CD25((-)) T(reg) cells. CD4(+)Foxp3(+) T(reg) cells displayed predominantly a central memory phenotype (CD45RA(-)CD27(+)), without differences between patients and healthy controls. Activated T(reg) cells were increased in HIV patients, particularly considering the central memory subset. In summary, HIV infection, but not HCV, induces an up-regulation of highly activated T(reg) cells, which increases in parallel with CD4 depletion. Hypothetically, this might contribute to the accelerated course of HCV-related liver disease in HIV-immunosuppressed patients.

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Figures

Fig. 1
Fig. 1
Representative example of flow cytometry. (a) Dot plots showing expression of forkhead box P3 (Foxp3) (left), CD25 (middle) and co-expression of both CD25 and FoxP3 (right) on CD4+ T cells. (b) Histograms showing the expression of CD127 on two different subsets of T regulatory (Treg) cells, CD25+ (left) and CD25– (right). (c) Dot plots showing the co-expression of CD45RA and CD27 on total CD4+ T cells (left) and on CD4+FoxP3+ Treg cells (right). (d) Histograms showing the expression of the activation marker CD38 on total CD4+ T cells (left) and on CD4+FoxP3+ Treg cells (right). FITC, fluorescein isothiocyanate; ECD, energy-coupled dye.
Fig. 2
Fig. 2
Percentages of T regulatory cells using three different phenotypic definitions [as CD4+ T cells expressing forkhead box P3 (FoxP3), CD25, or both FoxP3 and CD25] in four different groups of subjects: seronegative controls (open boxes), patients monoinfected with hepatitis C virus (light grey boxes), patients monoinfected with human immunodeficiency virus (HIV) (dark grey boxes) and patients co-infected with both HIV and HCV (solid boxes). (*) P < 0·05 with respect to HIV-infected patients.
Fig. 3
Fig. 3
Levels of CD127 expression on T regulatory cells expressing CD25 (open boxes) or not (grey boxes) in four different groups of subjects: seronegative controls, patients monoinfected with hepatitis C virus (HCV), patients monoinfected with HIV and patients co-infected with both human immunodeficiency virus and HCV. (*) P < 0·0001 with respect to CD25 negative T regulatory cells.
Fig. 4
Fig. 4
Maturation status of CD4+forkhead box P3 (Foxp3)+ T regulatory (Treg) cells according to CD45RA and CD27 expression in four different groups of subjects: seronegative controls (open boxes), patients monoinfected with HCV (light grey boxes), patients monoinfected with human immunodeficiency virus (HIV) (dark grey boxes) and patients co-infected with both HIV and hepatitis C virus (solid boxes). Vertical axis represents the proportion of Treg cells expressing each of the four different phenotypes. (*) P < 0·05 with respect to controls.
Fig. 5
Fig. 5
Level of CD38 expression on different subsets of CD4+forkhead box P3 (FoxP3)+ T regulatory cells and of CD4+ T lymphocytes in three different groups: seronegative controls (open boxes), patients monoinfected with hepatitis C virus (HCV) (light grey boxes) and patients infected with human immunodeficiency virus (co-infected or not with HCV, dark grey boxes). (*) P < 0·001 with respect to controls and HCV-monoinfected patients; (f) P < 0·005 with respect to total CD4+ T cells within the same group of subjects.
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