INCREASED TURNOVER OF HLA CLASS-I ANTIGENS IN PERIPHERAL-BLOOD MONONUCLEAR-CELLS FROM HIV-POSITIVE SUBJECTS

The level of soluble HLA class I (sHLA-I) molecules was determined in supernatants of peripheral blood mononuclear cell (PBMC) cultures from twelve HIV-positive asymptomatic subjects, from six subjects with AID S and from twenty HIV-negative healthy controls. The amount of sHLA-I molecules shed into supernatant by unstimulated PBMC from asymptomatic HIV-positive subjects (5.7 +/- 3.8 mu g/ml) and from subjects with AI DS (6.8 +/- 4.5 mu g/ml) was significantly higher (P = 0.07 and P = 0. 001, respectively) than that of unstimulated PBMC from HIV-negative su bjects (2.3 +/- 1.1 mu g/ml). The amount of sHLA-I molecules secreted into supernatant by phytohemagglutinin or anti-CD3 monoclonal antibody activated PBMC was significantly higher with respect to unstimulated PBMC. However, the amounts of sHLA-I molecules secreted by activated P BMC were comparable between HIV-positive and HIV-negative subjects. Th e elevated spontaneous shedding of sHLA-I molecules by unstimulated PB MC from HIV-positive subjects may reflect an accelerated turnover of H LA class I antigens in PBMC activated in vivo during HIV-1 infection a nd could contribute to the elevated sHLA-I antigen serum levels found in HIV-infected subjects. We suggest that in HIV-1 infection raised se rum levels of sHLA-I molecules may inhibit the cytotoxic activity of H LA class I restricted CD8(+) T cells that recognize HIV-1-infected CD4 (+) T cells and contribute to the dysregulation of immune responses in AIDS (Fund. Clin. Immunol. 3: 163-170, 1995).