PARADOXICAL INHIBITORY AND STIMULATORY EFFECTS OF HERPES SIMPLEX VIRUS (HSV) ON LYMPHOKINE-ACTIVATED KILLER (LAK) CELLS

Abstract

Strong LAK cell activity induced by interleukin-2 (IL-2) of cord (and adult) mononuclear cells (Pediatr. Res. 19: 271A, 1985) has suggested a possible role for LAK and/or IL-2 therapy in newborns with certain infections. The effect of HSV (type 1) on the LAK effector cell was studied by adding live or irradiated virus (10,000 R) (MOI=10) to 10 cells which have been incubated for 4-6 days with IL-2 (50-100 U/ml). The cells were tested 18-24 hrs later for cytotoxic activity against Cr-labelled K562 and Raji target cells. Live HSV inhibited LAK cytotoxicity of adult cells to K562 by 44% (72 ± 2.4%) to 40 ± 6.2%, n=15) and by 62% against Raji (50 ± 5.6% to 19 ± 4.4%). There was similar inhibition of cord LAK activity. Inhibition was dose dependent and independent of virus replication, since inhibition was observed with irradiated virus. The addition of live virus at the time of the cytotoxic assay or at the beginning of the IL-2 incubation did not affect LAK activity. By contrast, HSV stimulated cytotoxic activity against both targets in the absence of IL-2. The cytotoxicity of adult cells in the presence of live HSV (MOI=10) for 5-7 days increased from 3.3 ± 1.1% in the absence of virus and IL-2 to 19 ± 3.6% against K562 and from 2.2 ± 0.6% to 14 ± 4.4% against Raji targets (n=10). Cord cytotoxicity was stimulated but to a lesser degree.

In sum, HSV inhibits LAK effector cell activity independent of virus replication. Further, HSV alone induces natural cytotoxicity which may represent a unique antiviral defense system.

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