Mechanisms of autoimmunity and AIDS: prospects for therapeutic intervention.

The network theory of autoimmunity is presented with recent experimental data relevant to the understanding of the pathogenesis of AIDS. Schematically, effector T cells specific for self-antigens exist normally, but their activity is modulated and prevented by networks of regulatory T cells. As a result of mimicry between molecular components of microorganisms and self-antigens, autoimmune disease can be triggered by specific foreign pathogens which alter the state of activity of the network from suppression to activation. Conversely, by a procedure known as T-cell vaccination, autologous effector T cells re-injected after in vitro stimulation and attenuation may alter the state of the network from an activation to a suppression. Numerous observations are reviewed that support the concept of autoimmune activity in the destruction of non-infected T4 cells. Such activity is presumed to be triggered by an antigen of viral origin, the most likely, but not the only one, being the envelope protein gp 120. Based on this hypothesis, a T-cell vaccination procedure against effector T cells responsible for autoimmunopathic activity in HIV-seropositive patients is proposed, similar to the one known from experimental study of autoimmunity and presently being tested in human autoimmune diseases. Its purpose would be to prevent T-cell loss and the onset of immunodeficiency disease in HIV-seropositive patients. Apart from its potential therapeutic value, this procedure will have use as a therapeutic test from which insight will be gained about the immunopathogenesis of AIDS.

Can AIDS be prevented by T-cell vaccination?

T-cell vaccination as a specific prophylactic and therapeutic procedure has been shown to be effective in animal models of autoimmune disease. As autoimmunopathogenic components have been implicated in HIV infection, the authors propose a therapeutic test utilizing T-cell vaccination and suggest that AIDS could be prevented by such a procedure.

A defined basal medium for study of in vitro T-cell responses.

A basal serum-free medium has been devised which supports short-term murine T-cell proliferative and functional assays in the absence of added lipids or serum albumin. Immune responses obtained with this medium are totally dependent on cell-cell interactions known to generate the lymphokines and monokines essential for replication and differentiation. Background activity is minimal, allowing better control of the specificity of response than is possible with serum-containing media. This medium is also suitable for the identification of added agents which modulate immune responses, and may facilitate the purification of secreted factors.