Cycling of gut mucosal CD4+ T cells decreases after prolonged anti-retroviral therapy and is associated with plasma LPS levels - PubMed (original) (raw)

Cycling of gut mucosal CD4+ T cells decreases after prolonged anti-retroviral therapy and is associated with plasma LPS levels

E J Ciccone et al. Mucosal Immunol. 2010 Mar.

Abstract

The gut mucosa is an important site of HIV immunopathogenesis with severe depletion of CD4+ T cells occurring during acute infection. The effect of prolonged anti-retroviral therapy (ART) on cycling and restoration of T lymphocytes in the gut remains unclear. Colon and terminal ileal biopsies and peripheral blood samples were collected from viremic, untreated, HIV-infected participants, patients treated with prolonged ART (>5 years), and uninfected controls and analyzed by flow cytometry. In the gut, the proportion of cycling T cells decreased and the number of CD4+ T cells normalized in treated patients in parallel with beta 7 expression on CD4+ T cells in blood. Cycling of gut T cells in viremic patients was associated with increased plasma LPS levels, but not colonic HIV-RNA. These data suggest that gut T-cell activation and microbial translocation may be interconnected whereas prolonged ART may decrease activation and restore gut CD4+ T cells.

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Figures

Figure 1

The proportion and absolute number of (A) CD4+ and (B) CD8+ T cells in peripheral blood and gut compartments. Percentages are proportions of CD3+ T lymphocytes. Absolute numbers from gut are the number of cells per gram of biopsy tissue. Black bars indicate median values. Ileum values for the T cell percentages were not available for one VL<50 participant. Absolute number estimates were available for 7 HIV-, 13 No ART (10 for ileum), and 10 VL<50 (9 for ileum) patients.

Figure 2

The proportion of peripheral blood CD4+ T cells expressing (A) β7hi and (B) CCR5 in 9 HIV-, 9 No ART, and 11 VL<50 participants. The gating strategy in Part (C) was used to quantify expression of (D) β7hi and (E) CCR5 on effector (CD27-CD45RO+) and central (CD27+CD45RO+) memory CD4+ T cells. Black bars indicate median values.

Figure 3

Comparison of the associations between peripheral blood (A, D) CD4+β7hi, (B, E) CD4+CCR5+, and (C, F) CD4+ T cells and the (A-C) percentage and (D-F) absolute number of CD4+ T cells in colon and terminal ileum. Filled symbols represent colon values, and open symbols reflect terminal ileal values. Spearman rank correlations for comparisons of all three groups and HIV+ groups only are displayed below each graph.

Figure 4

The percentage of cycling (A) CD4+ and (B) CD8+ T cells (Ki67+) in peripheral blood and gut compartments. Included in the analysis are participants who had Ki67 subset information for both PB and colon (8 HIV-, 7 No ART and 10 VL<50). Of these individuals, ileum measurements were not available for one No ART and two VL<50 participants. Black bars indicate median values.

Figure 5

(A) Plasma levels of LPS and sCD14 in 7 HIV- (blue triangles), 9 No ART (red diamonds), and 12 VL<50 (black circles) individuals. Black bars indicate median values. (B) Correlation between LPS levels and the percentage of CD4+Ki67+ and CD8+Ki67+ T cells in peripheral blood (left column), colon (middle column), and ileum (right column). Colon values were not available for an additional two participants from each group. Spearman rank tests were used to determine correlation and p-values.

References

1. Lapenta C, Boirivant M, Marini M, Santini SM, Logozzi M, Viora M, et al. Human intestinal lamina propria lymphocytes are naturally permissive to HIV-1 infection. Eur J Immunol. 1999 Apr;29(4):1202–8. - PubMed
1. Anton PA, Elliott J, Poles MA, McGowan IM, Matud J, Hultin LE, et al. Enhanced levels of functional HIV-1 co-receptors on human mucosal T cells demonstrated using intestinal biopsy tissue. AIDS. 2000 Aug 18;14(12):1761–5. - PubMed
1. Poles MA, Elliott J, Taing P, Anton PA, Chen IS. A preponderance of CCR5(+) CXCR4(+) mononuclear cells enhances gastrointestinal mucosal susceptibility to human immunodeficiency virus type 1 infection. J Virol. 2001 Sep;75(18):8390–9. - PMC - PubMed
1. Mehandru S, Poles MA, Tenner-Racz K, Horowitz A, Hurley A, Hogan C, et al. Primary HIV-1 infection is associated with preferential depletion of CD4+ T lymphocytes from effector sites in the gastrointestinal tract. J Exp Med. 2004 Sep 20;200(6):761–70. - PMC - PubMed
1. Schnittman SM, Lane HC, Greenhouse J, Justement JS, Baseler M, Fauci AS. Preferential infection of CD4+ memory T cells by human immunodeficiency virus type 1: evidence for a role in the selective T-cell functional defects observed in infected individuals. Proc Natl Acad Sci U S A. 1990 Aug;87(16):6058–62. - PMC - PubMed

Cycling of gut mucosal CD4+ T cells decreases after prolonged anti-retroviral therapy and is associated with plasma LPS levels - PubMed (original) (raw)