THE LEUKOCYTE FUNCTION-ASSOCIATED ANTIGEN-1 (LFA-1) IS INVOLVED IN THE INTERFERON-ALPHA RESPONSE INDUCED BY HERPES-SIMPLEX VIRUS IN BLOOD LEUKOCYTES

The role of the leukocyte function-associated antigen-I (LFA-1) family of integrins (beta2 integrins) in the interferon-alpha (IFN-alpha) re sponse was examined, using human peripheral blood mononuclear cells (P BMCs) stimulated in vitro by glutaraldehyde-fixed Herpes simplex virus -infected WISH amnion cells. Monoclonal antibodies (mAbs) to the beta2 chain (CD18) and to the alpha chain of LFA-1 (CD11a) reduced the numb er of IFN-alpha-producing cells (IPCs) by 30-50%, but mAbs to CD11b or c caused no inhibition. The IB4 mAb to CD18 was inhibitory when added during the first 2 h of the IFN-alpha response, but did not alter its kinetic. In contrast, the IB4 prevented the early enhancement of the IFN-alpha response caused by addition of interleukin-3 (IL-3) or granu locyte-macrophage colony-stimulating factor (GM-CSF). However, a delay ed down-regulation of the IPC response occurred in such PBMC cultures, and a paradoxical increase in the total production of IFN-alpha. The results suggest that LFA-1 (CD11a/CD18) participates in the early phas e of the IFN-alpha response and may be activated by cytokines such as IL-3 and GM-CSF.