Lymphocyte-reactive autoantibodies in human immunodeficiency virus type 1-infected persons facilitate the deletion of CD8 T cells by macrophages.

Abstract

The number of peripheral blood CD8 T cells declines in advanced stages of human immunodeficiency virus (HIV) infection coinciding with the transition from a clinically asymptomatic state of infection to AIDS. Although blood monocytes/macrophages exhibit cytotoxicity for CD4 T cells soon after HIV infection, cytotoxicity against CD8 T cells occurs at the time when HIV infection advances. The cytotoxic reaction is mediated by immunoglobulins that bind to T cells and which can be eluted from them. The immunoglobulins enable macrophages from noninfected persons to destroy healthy T cells in tissue culture. Lymphocyte-reactive autoantibodies (LRAs) occur physiologically as a result of chronic allo- or self-antigen stimulation. Lymphopenic, autoimmune lupus erythematosus patients exhibit LRAs that facilitate the deletion of T cells by macrophages. It is proposed that LRAs represent an immunoregulatory cytotoxic mechanism that is activated after chronic immune stimulation and is engaged by HIV to deplete host lymphocytes.