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NLM AIDSLINE
Host factors in the pathogenesis of HIV disease.
Fauci AS; NAID, NIH, Bethesda, MD.
November 30, 1996
3rd Conf Retro and Opportun Infect. 1996 Jan 28-Feb 1;:170. Unique

The pathogenic mechanisms of human immunodeficiency virus (HIV) disease are determined by an interplay of virus and host factors. Among the host factors contributing to the immunopathogenic mechanisms are the specific immune response to the virus, particularly the expansion of restricted subsets of CD8+ T cells following primary HIV infection; the degree and persistence of immune activation; and the expression of a variety of immunoregulatory and pro-inflammatory cytokines. We have established that cytokines such as TNF-alpha, IL-1beta, and IL6 are overexpressed in lymphoid tissue and are capable of potently inducing HIV expression. Of note is the fact that endogenous cytokines tightly control HIV expression and virus replication can be markedly downregulated by blocking the autocrine cytokine pathways. In contrast, CD8+ supressor T cells can potently block HIV expression in a non cytolytic manner. We have demonstrated that IL-2 can selectively induce expression on CD8+ T cell supressor function and that this effect overrides the ability of IL-2 to support HIV expression. This phenomenon will be discussed, particularly in light of the recent report from our laboratory that intermittent infusions of IL-2 into HIV infected individuals have led to substantial and sustained elevations of CD4+ T cells in the majority of such individuals, especially those in whom immune suppression is not yet far advanced. We will also discuss the effects on various in vitro model systems of recently identified CD8+ T cell derived cytokines that inhibit HIV expression of HIV and how an activated immune system may be more susceptible to the initiation and propagation of HIV infection.

CD8-Positive T-Lymphocytes/IMMUNOLOGY Cytokines/GENETICS HIV Infections/BLOOD/*IMMUNOLOGY/PHYSIOPATHOLOGY Human T-Lymphocyte Subsets ABSTRACT

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