The Leukocyte Function-Associated Antigen-1 (LFA-1) Is Involved in the Interferon-α Response Induced by Herpes Simplex Virus in Blood Leukocytes

Abstract

The role of the leukocyte function-associated antigen-1 (LFA-1) family of integrins (β₂ integrins) in the interferon-α (IFN-α) response was examined, using human peripheral blood mononuclear cells (PBMCs) stimulated in vitro by glutaraldehyde-fixed Herpes simplex virus-infected WISH amnion cells. Monoclonal antibodies (mAbs) to the β₂ chain (CD18) and to the α chain of LFA-1 (CD11a) reduced the number of IFN-α-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-α response, but did not alter its kinetic. In contrast, the IB4 prevented the early enhancement of the IFN-α response caused by addition of interleukin-3 (IL-3) or granulocyte-macrophage colony-stimulating factor (GM-CSF). However, a delayed down-regulation of the IPC response occurred in such PBMC cultures, and a paradoxical increase in the total production of IFN-α. The results suggest that LFA-1 (CDlla/CD18) participates in the early phase of the IFN-α response and may be activated by cytokines such as IL-3 and GM-CSF.