Mucosal T-cell responses to HIV: responding at the front lines

Abstract

Mucosal surfaces of the body serve as the major portal of entry for human immunodeficiency virus (HIV). These tissues also house a majority of the body's lymphocytes, including the CD4(+) T cells that are the major cellular target for HIV infection. Mucosal surfaces are defended by innate and adaptive immune mechanisms, including secreted antibodies and CD8(+) cytotoxic T cells (CTL). CTL in mucosal lymphoid tissues may serve to limit viral replication, decreasing the host's viral burden as well as reducing the likelihood of sexual transmission to a naïve host. This review summarizes recent literature on HIV-specific T-cell responses in mucosal tissues, with an emphasis on the gastrointestinal tract.

Figure 1. Mucosal CD8+ T-cells

The figure shows an idealized rectal mucosa, with a single layer of columnar epithelium. HIV-1 may enter the mucosa through breaches in the epithelial layer (1); by binding to dendritic cell processes that extend through the epithelial layer to the lumen (2); via transcytosis across epithelial cells (3); or through a combination of mechanisms. CD8+ T-cells are present as intraepithelial cells (IEL) located between epithelial cells, and in the underlying layer as lamina propria lymphocytes (LPL). Also present in the lamina propria are CD4+ T-cells, macrophages, and antibody-producing plasma cells.

Figure 2. Nine-color, 5-function analysis of HIV Gag-specific T-cell responses in rectal mucosa

The figure summarizes data for one patient, an HIV controller whose Gag-specific CD8+ T-cell response is substantially stronger (in terms of percent responding cells) and more polyfunctional in rectal mucosa than in blood. Bar graphs show the magnitude of the Gag-specific response in each of 31 functional categories. The legend shows the combination of functions evaluated in each category. These combinations are color-coded based on the number of functions and correspond to wedges in the pie charts (5-function responses are black, 4-function red, 3-function orange, 2-function yellow, and single-function white). The rectal Gag-specific CD8+ T-cell response (white bars) of this HIV controller was heavily biased towards polyfunctional cells secreting CD107, MIP-1β, TNF-α and IFN-γ. In contrast, the Gag-specific response in PBMC was largely monofunctional. Data for over 20 HIV controllers, compared to non-controllers and patients on HAART, are reported elsewhere [62, 63].