The Journal of Immunology, Vol 136, Issue 10 3619-3624, Copyright © 1986 by American Association of Immunologists

ARTICLES

Analysis of effector mechanisms against HTLV-I- and HTLV-III/LAV- infected lymphoid cells

FW Ruscetti, JA Mikovits, VS Kalyanaraman, R Overton, H Stevenson, K Stromberg, RB Herberman, WL Farrar and JR Ortaldo

Acquired immunodeficiency syndrome is associated with a viral (HTLV- III/LAV)-mediated progressive depletion of a helper/inducer T4+ T cell subset, whereas acute T cell leukemia is associated with a viral (HTLV- I)-mediated growth of the same T cell subset. Because large granular lymphocytes (LGL) with natural killer (NK) activity have been shown to spontaneously lyse several virus-infected target cells, the ability of NK cells to lyse both HTLV-I- and HTLV-III/LAV-infected lymphoid cell lines and fresh lymphocytes was explored. Normal lymphocytes (T cells and LGL), with and without pretreatment with recombinant interleukin 2 (IL 2), as well as monocytes, with and without pretreatment with interferon-gamma were employed as effectors. Both IL 2-activated T cells and NK cells were cytolytic for HTLV-I-infected targets. However, only LGL demonstrated significant spontaneous activity against HTLV-I- infected targets. Similarly, LGL showed spontaneous cytolytic activity against HTLV-III/LAV-infected targets, and this cytotoxicity was considerably augmented by IL 2. In contrast, T cells and monocytes were unable to lyse HTLV-III/LAV targets, and only minimal activity was induced by activation. LGL cells, B cells, and monocytes were infectible in vitro by high titers of HTLV-III/LAV. However, levels of reverse transcriptase found in these cultures were significantly lower than the levels in T cell cultures. In contrast, only T cells were susceptible to infection by HTLV-I. Experiments with the use of cell cocultures showed that LGL afforded T cells protection from infection by HTLV-I (as indicated by lack of transformation and viral protein expression) but not from infection by HTLV-III/LAV. Collectively, these results indicate that NK cells may play a role in protecting cells against HTLV infection.

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