AEGiS-11IAC: Persistent immune activation and the pathogenesis of AIDS - lessons from the Ethiopian immigration to Israel.

11th International AIDS Conference

Vancouver, British Columbia — July 7-12, 1996

Persistent immune activation and the pathogenesis of AIDS - lessons from the Ethiopian immigration to Israel.

Int Conf AIDS 1996 Jul 7-12; 11:15 (abstract no. We.A.503)
Bentwich Z, Kalinkovich Z, Weisman Z, Grossman Z; Ruth Ben Ari Institute of Clinical Immunology, Kaplan Hospital, Rehovot, Israel. Fax: 972-8-941-0461.

Background: We have previously proposed that several of the manifestations of HIV infection reflect the chronicity of the infection rather than dysregulation of the immune system, unique to HIV. This proposition is based the tunable-activation threshold hypothesis (Grossman & Paul, PNAS, 89:10365, 1992), which implies that the immune response to chronic infection is qualitatively distinct from the response to acute infection. The recent immigration of HIV-infected (HIV+) and non-infected (HIV-) Ethiopians (ET), found to be immune activated by chronic infections primarily helminthic, has enabled us to test and confirm some of these ideas.

OBJECTIVES: Study the immune features of chronically activated HIV(-) hosts, their susceptibility to HIV infection, and the effect HIV infection has on these elements.

RESULTS: 1) The immunologically activated HIV(-) ET, have several features of HIV(+) individuals: inverted CD4/CD8 ratio, increased CD8+ memory sells, decrease naive cell numbers and cell activation without proliferation. 2) Susceptibility to HIV infection of PBMC was not increased in HIV(-) ET, probably reflecting a balance between distinct modes of cellular activation - activated susceptible CD4 cells and strongly suppressive elements (CD8 cells and factors). 3) In the HIV(+) ET a more pronounced suppression of cytokine secretion, compared to HIV(+) Israelis was observed.

CONCLUSIONS: a) Chronic immune activation in itself may account for several immunological changes seen in HIV infection. b) The role of HIV in pathogenesis of AIDS may be primarily due to its potent and persistent stimulation of the immune system. c) Hosts sustaining other infections in addition to HIV, cope differently with HIV infection and should therefore be addressed differently for protective vaccine design and for immunotherapy.

Keywords: AEGIS, Acquired Immunodeficiency Syndrome, HIV Infections, Emigration and Immigration, Lymphocyte Activation, HIV Seronegativity, Immunologic Memory, Immunity, Ethiopia, Africa, Israel, immunology, ICA11

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