8th International AIDS Conference Amsterdam, Netherlands — July 19-24, 1992

Int Conf AIDS 1992 Jul 19-24; 8:We53 (abstract no. WeA 1047)
Shearer G, Clerici M; Experimental Immunology Branch, NCI, National Institutes of Health, Bethesda, MD 20892.

OBJECTIVES: To determine whether alterations in the function of TH1 and TH2 helper cells are present in HIV infection.

METHODS: Interleukin-2 (IL-2) and interleukin-4 (IL-4) cytokines were measured in antigen-and mitogen-stimulated peripheral blood leukocytes (PBL) of human immunodeficiency virus seropositive (HIV+) individuals using bioassays with either the IL-2 dependent CTLL or the IL-4 dependent cell line CT.h4S (gift of Dr. W. E. Paul, Laboratory of Immunology, NIAID, NIH).

RESULTS: 45 HIV+ patients were studied for IL-2 and IL-4 production. Three different functional patterns were recognized: (1) high IL-2 and low IL-4 (n = 16); (2) low IL-2 and high IL-4 (n = 19) and (3) low IL-2 and low IL-4 (n = 10). All HIV-controls (n = 18) exhibited a type (1) profile. Reciprocal patterns of lymphokine production could be shown as IL-2:IL-4 ratios, with the highest ratio in group (1) (2.12) and progressively decreasing ratios for groups (2) (0.08) and (3) (0.3). The IL-2:IL-4 ratio in PBL from HIV- controls was 5.54. A longitudinal study of an HIV+ individuals indicated a sequential cytokine profile such that: (1)----(2)----(3). Antigenic stimulation of PBL from HIV+ individuals in (2) in the presence of an anti-IL-4 antibody restored TH1 function.

CONCLUSIONS: We suggest a progressive change in TH function after HIV infection, such that the first TH1 greater than TH2 stage, which may be more protective and is characteristic of healthy uninfected individuals, is followed by a second stage in which TH2 greater than TH1 with TH2 producing IL-4 and, finally by a more severe stage of TH dysfunction in which greatly reduced levels of both IL-2 and IL-4 are observed. The mechanism responsible for this phenomenon is under investigation, and may involve TH1-TH2 cytokine cross-regulation, in which IL-10 could play an important role.

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