Mechanisms of autoimmunity and AIDS: prospects for therapeutic intervention

Abstract

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.

AIDS Vaccines and Reproductive Immunology

“…In fact the concept of alloimmunization for HIV indication has been promoted by many research groups for more than a decade but it has never received due consideration [39][40][41][42][43]. It is hoped that the new experimental evidence that became available recently will change this situation.…”

“…Indeed, the vaccination with alloantigens as the immune basis for preventive vaccination has been advocated by many reputable immunologists [36][37][38][39][40][41][42][43]. The positive data from Abalaka's experiments and placebo-controlled trial results with V-1 Immunitor suggest that allovaccination has good chances of success and needs to be investigated further [49,50,61].…”

Therapeutic AIDS Vaccines

“…The opinion that AIDS is an autoimmune disease and alloimmunization is perhaps the answer to the problem has been expressed by many researchers over the last two decades [150][151][152][153][154][155][156][157][158][159]. If it is correct, then the prevailing AIDS vaccine strategy, which is directed away from the alloimmunization concept, may be flawed.…”

T-cell vaccination against anti-CD4 autoimmunity in HIV-1 infected patients

“…T-cell vaccination has been studied in experimental animals (Ben-Nun et al, 1981;Cohen, 2000;Lider et al, 1988), and lately has been used clinically to induce the downregulation of human autoimmune diseases such as multiple sclerosis (Zhang et al, 1993;Cohen, 2002;Zhang et al, 1995Zhang et al, , 2000. Atlan and colleagues have previously suggested that autologous anti-CD4 T-cells might be used as vaccines to down-regulate anti-CD4 autoimmunity in HIVinfected patients (Atlan et al, 1993(Atlan et al, , 1994Atlan and Cohen, 1996).…”