Combined Action of Anti-CD4 Autoantibodies and Rheumatoid Factor in the Development of CD4 Lymphocytopenia in Rats Immunized with HIV-1 gp120.

The development of immunodeficiency in HIV-infected patients is known to result from CD4 lymphocyte depletion. Most CD4 lymphocyte cells destined to die are not infected. The mechanism of HIV-uninfected cell death has not yet been fully elucidated. The aim of this study is to examine the role of anti-CD4 autoantibodies and physiological rheumatoid factor (RF) in the development of CD4 lymphocytopenia. Immunization of Wistar rats with gp120 HIV-1 induces chronic production of anti-CD4 autoantibodies and decreases CD4 lymphocytes in the blood. However, the anti-CD4 autoantibodies produced as part of the immune response to gp120 do not kill CD4 cells directly. In rats producing anti-CD4 autoantibodies, a low level of peripheral CD4 lymphocytes is associated with high blood RF levels. The sera containing RF killed lymphocytes when the lymphocytes were pretreated with sera containing anti-CD4 autoantibodies. Thus, the death of CD4 lymphocytes in rats immunized with gp120 is a result of the combined action of anti-CD4 autoantibodies and RF, and the action of these factors can be separated in time. The fact that two signals are needed for CD4 lymphocyte death in HIV gp120-immunized rats does not contradict the hypothesis of the activation-induced death of uninfected CD4 cells in HIV-infected humans.