IMPAIRMENT OF MONOCYTIC FUNCTION AFTER INFLUENZA-VIRUS INFECTION

In order to analyze the immunosuppression associated with influenza vi rus infection, we investigated monocytic function in macrophage hybrid oma cell lines 5 weeks after infection with two strains of influenza v irus. Clones 30 and 63, chosen for stability in long-term culture, wer e infected with two strains of influenza virus, X-31 and PR-8. Uniform infection of both cell lines was confirmed by intracytoplasmic staini ng with the antihemagglutinin strain-specific monoclonal antibodies PY 102 and PY 206. One week after infection, clones 30 and 63 lost their ability to stimulate tetanus toxoid-specific major histocompatibility complex (MHC)-matched responder T cells. Coincident with the inabilit y to stimulate MHC-matched T cells, there was diminished surface expre ssion of class II MHC antigens and LFA-1-alpha and LFA-3 compared with that in uninfected cells: DR, 2.5 versus 10.6% (mean channel 0.3 vers us 1.5); DQ, 1.6 versus 15.6% (mean channel 0.3 versus 3.0); DP, 5.0 v ersus 30.9% (mean channel 0.3 versus 2.0). LFA-1-alpha expression was reduced (13.1 versus 20.0%; mean channel 1.5 versus 2.0) while LFA-3 e xpression remained the same (22.2 versus 324%; mean channel 3.0 versus 3.3), Class I MHC surface antigen expression was unaltered. Cytokine secretion was also perturbed, as interleukin 1-alpha (IL-1-alpha) and IL-1-beta production was lost 1 week after infection, Production of IL -12 and IL-10 was unchanged, while IL-6 production was increased. The viability of the T cells cocultured with 63(Flu) was unaltered, demons trating that the inability of the MHC-restricted T cells to proliferat e in response to tetanus toroid wits not due to a toxic effect of 63(F lu). Interestingly, other accessory functions, including the ability t o support mitogen- and anti-CD3-mediated T-cell proliferation, remaine d intact, These data suggest that alteration of macrophage function re lating to viral infection occurs at multiple levels and may contribute to the immunosuppression observed following influenza virus infection .