CD57 expression by T cells in the female genital tract of HIV-zx1 infected women

Abstract

Despite an influx of T cells to the cervix during HIV infection, genital T cells are not associated with control of HIV shedding. CD57 expression by T cells has been associated with enhanced migratory potential and CD57+ T cells have been shown to accumulate in tissues during the late stages of HIV disease. We investigated the impact of HIV-infection and clinical status on the expression of CD57 by T cells from the female genital tract in 13 HIV-infected and 5 uninfected women. We found that cervical and blood-derived T cells expressed similar frequencies of CD57. The frequency of CD57 expression by cervical or blood T cells was not associated with clinical status (CD4 counts). No impairment in IFN-gamma production by CD57+ T cells from the genital tract was observed. We conclude that increased T cell senescence does not appear to be a hallmark of genital mucosal HIV-1 infection.

Figure 1

Expression of CD57 by CD8+ and CD4+ T cells derived from the cervix and blood of HIV+ and HIV− women. (A) Representative plots showing the frequency of CD57 expression by blood (left panels) and cervical (right panel) CD8+CD3+ (top panels) and CD4+CD3+ (lower panels) T cells. (B) We compared the frequency of CD57+ expression by CD8+CD3+ (upper panel) and CD4+CD3+ (lower panel) T cells in blood and cervical T cells from HIV− (n = 5) and HIV+ (n = 13) women. Each dot represents an individual woman's CD57 frequency and lines joining dots indicate matched blood and cervical frequencies in individual woman. Paired Student's t-test was used to compare CD57 expression frequencies in blood and at the cervix. An unpaired Student's t-test was used to compare CD57 expression frequencies in HIV+ and HIV− women. (C) Association between the frequency of CD57 expression by cervical and blood-derived CD8+CD3+ (left panel) and CD4+CD3+ (right panel) T cells. Regression lines and Pearson R-values are shown for correlations. p-values ≤ 0.05 were considered significant.

Figure 2

Comparison of CD95, CD28 and CD38 expression by CD57+ T cells in the female genital tract and blood. (A) Representative plots showing the frequency of CD57 expression by cervical (top panels) and blood (right panel) CD8+CD3+ T cells co-expressing CD95 (left panels), CD28 (middle panels) or CD38 (right panels). (B) Association between the frequency of CD57 expression by cervical (top panels) and blood-derived (bottom panels) T cells and CD95 expression (left panels), lack of CD28 expression (CD28−; middle panels) and CD38 expression (right panels). Regression lines and Spearman Rho-values are shown for correlations. p-values ≤ 0.05 were considered significant.

Figure 3

Comparison of ex vivo IFN-γ production by CD57+ and CD57− T cells derived from the blood and genital mucosa of HIV− and HIV+ women in response to polyclonal stimulation (PMA/ionomycin). (A) Representative plots showing the frequency of IFN-γ production by CD57+ or CD57− CD8⁺ T cells in the blood (left panels) and cervix (right panels) following PMA/ionomycin stimulation. (B) Net percentages of IFN-γ producing CD57+CD8+ and CD57−CD8+ T cells (percentage of stimulated IFN-γ producing cells minus the percentage of background percentage of unstimulated cells producing IFN-γ) after ex vivo stimulation with PMA/ionomycin were compared in cervical mucosa (upper panel) and blood (lower panel) in HIV− (left panel) and HIV+ (right panel) women. (C) Net percentages of IFN-γ producing CD57+CD4+ and CD57−CD4+ T cells in cervical mucosa (upper panel) and blood (lower panel in uninfected (left panel) in HIV− and HIV+ (right panel) women. Each dot represents an individual's net percentage of CD57+CD8+ or CD57−CD8+ T cells producing IFN-γ at the cervix and in blood. p-values ≤ 0.05 were considered significant. Paired Student's t-test was used to compare IFN-γ frequencies by CD57+ versus CD57− T cells per individual.

Figure 4

Comparison of ex vivo IFN-γ production by CD57+ and CD57− T cells derived from blood and the genital mucosa of HIV+ and HIV− women in response to stimulation with HIV Gag peptides (Du422 Subtype C). (A) Net percentages of CD57+CD8+ T cells in HIV+ women (n = 18) producing IFN-γ (percentage stimulated IFN-γ producing cells minus the percentage of unstimulated cells producing IFN-γ) after ex vivo stimulation with HIV Gag peptides were compared in blood (upper panel) and at the cervical mucosa (lower panel). (B) Net percentage of CD57−CD8+ T cells from HIV+ women producing IFN-γ in blood (upper panel) and at the cervix (lower panel). Each bar represents an individual's net percentage IFN-γ producing CD57+CD8+ or CD57−CD8+ T cells at the cervix and in blood. (C) Association between the net percentages of CD57+CD8+ and CD57−CD8+ cells producing IFN-γ in response to Gag in the blood (upper panel) and at the cervix (lower panel). Each dot represents an individual woman's net IFN-γ producing CD57+ and CD57− T cell frequencies in blood and at the cervix. Regression lines and Spearman Rho values are shown for correlations. p-values ≤ 0.05 were considered significant. Wilcoxon matched pairs tests were used to compare frequencies of IFN-γ producing CD57+ and CD57− T cells within and between compartments.