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.

This assay will prove useful for the detection of memory T cells present at low frequency, and may be of interest for identifying subdominant cytotoxic T lymphocyte epitopes. This method may have broad applications for the detection of antiviral CD8 T cell responses in patient populations in whom such responses have been difficult to detect, including HIV-1-seropositive individuals with advanced disease or undergoing HAART.

In the Heterosexual AIDS Transmission Study (HATS), the frequency of high-risk sexual activity and viral load in the seropositive partner were shown to correlate with HIV-1 transmission. However, these parameters could not account for the status of some exposed, seronegative (ESN) individuals who remained uninfected despite years of exposure. To test the hypothesis that antiviral immune responses are a correlate of nontransmission in this cohort, we developed two sensitive methods for assessing HIV-1-specific humoral and cell-mediated responses. To quantify T cell responses, autologous mature dendritic cells (DCs) were used as antigen-presenting cells to elicit HIV-1-specific IFN-gamma production by ELISPOT. Antibody responses to HIV-1 gp120 were assessed by combination immunoprecipitation-Western blot (IP-WB). Previous studies of this cohort, using limiting dilution analysis, did not reveal HIV-1-specific cytotoxic T lymphocyte activity. However, when autologous DCs were used to present HIV-1 antigens, T cells from three of eight ESN women (38%) responded by producing IFN-gamma. T cells from three of four seropositive partners responded to HIV-1 antigens, whereas five negative controls did not. The use of DCs as antigen-presenting cells increased sensitivity by 2- to 30-fold relative to standard ELISPOT. Using IP-WB, low levels of gp120-reactive antibodies were detected in plasma from 1 of 14 ESN women. These results support the hypothesis that HIV-1-specific T cell responses play a role in immune surveillance in this cohort of North American serodiscordant couples. This report also demonstrates the ability of dendritic cells to reveal T cell responses that might be overlooked by other methods.