Figure 1.

The Figure shows idealized drawings of rectal mucosa in uninfected individuals (left), HIV non-controllers (NC, center), and HIV controllers (C, right). Individual cell types are identified in the legend. For simplicity, innate effector cells such as natural killer (NK) cells and TCR-gamma delta cells are not shown. Major differences between groups include: (1) CD4+ T-cells are severely depleted in NC, but relatively well preserved in C. Mucosal CD4+ T-cells in C (but not NC) include significant populations of HIV-specific, polyfunctional cells that act in synergy with CD8+ T-cells. (2) CD8+ T-cells are abundant in both NC and C, but the proportion of HIV-specific, polyfunctional CD8+ T-cells is higher in C. (3) HIV virus production is high in the GI tract of NC; however, despite low levels of plasma viremia, controllers likely also have detectable virus in gut tissue, as suggested by studies in the SIV model. (4) Intestinal epithelial barrier integrity is severely compromised in NC, but to a much lesser extent in C. (5) Immune activation leads to deposition of collagen in lymphoid tissues of NC, potentially limiting CD4+ T-cell reconstitution. Controllers also have elevated markers of immune activation as compared to HIV negative individuals, but significantly lower than NC. (6) Regulatory T-cells are positively correlated with immune activation, and are present at higher frequency (as % of total CD4+ T-cells) in NC than C. In summary, these three groups represent a continuum with HIV controllers showing less barrier impairment, lower immune activation, and stronger, more polyfunctional HIV-specific T-cell responses than non-controllers.