Significantly skewed memory CD8+ T cell subsets in HIV-1 infected infants during the first year of life

Abstract

HIV-1 infection causes a severe T cell compromise; however, little is known about changes in naive, memory, effector and senescent T cell subsets during the first year of life. T cell subsets were studied over the first year of life in blood from 3 infant cohorts: untreated HIV-infected, HIV-exposed but uninfected, and HIV-unexposed. In HIV-infected infants, the frequency of CCR7(+)CD45RA(+) naive CD8(+) T cells was significantly decreased, while the frequency of CCR7(-)CD45RA(-) effector memory CD8(+) T cells was increased, compared with the control cohorts. A larger population of CD8(+) T cells in HIV-infected infants displayed a phenotype consistent with senescence. Differences in CD4(+) T cell subset frequencies were less pronounced, and no significant differences were observed between exposed and unexposed HIV-uninfected infants. We concluded that the proportion of naive, memory, effector and senescent CD8(+) T cells during the first year of life is significantly altered by HIV-1 infection.

Figure I

Frequencies of total CD4⁺ T cells (A) and CD8⁺ T cells (B), among total T cells and CD4/CD8 ratios (C), in the peripheral blood of infants from the HIV⁺, HIV⁻ Exposed, or HIV⁻ groups, over the first year of life, measured by flow cytometry. Boxes in boxplots represent medians and interquartile ranges, with the total range as the whiskers. Differences: *p < 0.05; **p < 0.01; ***p< 0.001, Kruskal-Wallis test, with Dunn’s Multiple Comparison Test.

Figure II

Frequencies and absolute numbers of CD8⁺ T cell memory populations defined by CD45RA and CCR7, or CD45RA and CD62L, expression in peripheral blood of the 3 groups of infants, measured by flow cytometry. (A) Gating strategy: Lymphocytes were selected for by setting a lymphocyte gate according to FSC and SSC profiles, and CD8 T cells included by selecting CD3+ CD8+ cells. The phenotype of CD8+ T cells was assessed by gating on the CD3+CD8+ T cells, and analysing either CD45RA/CCR7 staining or CD45RA/CD62L staining. (B) Dotplots shown for CCR7 and CD45RA staining from 3 representative infants. (C–D) Median frequencies of each subset. (E–F) Median absolute numbers of each subset. CD62L/CD45RA staining is only depicted when this differed from CCR7/CD45RA staining. Differences: *p < 0.05; **p < 0.01; ***p< 0.001, Kruskal-Wallis test, with Dunn’s Multiple Comparison Test. The distributions are shown in Supplementary Figures I and II.

Figure III

Frequencies and absolute numbers of CD4⁺ T cell memory populations defined by CD45RA and CCR7, or CD45RA and CD62L, expression in peripheral blood of the 3 groups of infants, measured by flow cytometry. (A) Dotplots from 3 representative infants. (B–C) Median frequencies of each subset. (D–E) Median absolute numbers of each subset. CD62L/CD45RA staining is only depicted when this differed from CCR7/CD45RA staining. Gating strategy: Lymphocytes were selected for by setting a lymphocyte gate according to FSC and SSC profiles, and CD8 T cells included by selecting CD3+ CD8+ cells. The phenotype of CD8+ T cells was assessed by gating on the CD3+CD8+ T cells, and analysing either CD45RA/CCR7 staining or CD45RA/CD62L staining. Differences: *p < 0.05; **p < 0.01; ***p< 0.001, Kruskal-Wallis test, with Dunn’s Multiple Comparison Test. The distributions are shown in Supplementary Figures III and IV.

Figure IV

Absolute numbers of CD8⁺ T cells expressing CD57 (A) and CD28 (B) in peripheral blood of the 3 infant groups, measured by flow cytometry. Boxes in boxplots represent medians and interquartile ranges, with the total range as the whiskers. Gating strategy: Lymphocytes were selected for by setting a lymphocyte gate according to FSC and SSC profiles, and CD8 T cells included by selecting CD3+ CD8+ cells. The phenotype of CD8+ T cells was assessed by gating on the CD3+CD8+ T cells, and analysing either CD57 expression or CD28 expression. Differences: *p < 0.05; **p < 0.01; ***p< 0.001, Kruskal-Wallis test, with Dunn’s Multiple Comparison Test.