Increased adhesion molecule and chemokine receptor expression on CD8+ T cells trafficking to cerebrospinal fluid in HIV-1 infection.

BACKGROUND

The central nervous system (CNS) is a recognized target for human immunodeficiency virus type 1 (HIV-1). CD8(+) T cells may mediate viral clearance from the CNS but also may contribute to immune-mediated neuronal damage.

METHODS

Using 4- and 6-color flow cytometry, we investigated the role of adhesion molecules (very late antigen [VLA]-4 [ alpha 4 beta 1 integrin] and leukocyte function antigen [LFA]-1 [ alpha L beta 2 integrin]) and chemokine receptors (CXCR3 and CCR5) in CD8(+) T cell migration to cerebrospinal fluid (CSF) during HIV-1 infection.

RESULTS

CD8(+) T cells trafficking to CSF were uniformly VLA-4(high), LFA-1(high). CCR5 expression was significantly enhanced in T cells from CSF, compared with those from blood (P<.001), including HIV-1-specific CD8(+) T cells, and most T cells from CSF expressed both CXCR3 and CCR5. Interferon-inducible protein (IP)-10 (CXCL10) levels in CSF were significantly increased in HIV-1-positive individuals, relative to IP-10 levels in control subjects (P=.007), and a positive correlation was found between IP-10 levels and virus load in CSF (r2=.777; P=.0007).

CONCLUSIONS

These findings suggest that LFA-1, CCR5 and CXCR3, and IP-10 play an important role in lymphocyte trafficking to CSF during HIV-1 infection. These observations suggest a "push-pull" model, in which lymphocyte extravasation is driven by lymphocyte activation, expression of adhesion molecules, and increased vascular permeability and is coupled with chemokine-mediated trafficking to inflammatory sites in the CNS.