T-CELL-DEPENDENT ACTIVATION OF MACROPHAGES AND ENHANCEMENT OF THEIR PHAGOCYTIC-ACTIVITY IN THE LUNGS OF MICE INOCULATED WITH HEAT-KILLED CRYPTOCOCCUS-NEOFORMANS - INVOLVEMENT OF IFN-GAMMA AND ITS PROTECTIVE EFFECT AGAINST CRYPTOCOCCAL INFECTION

Previous investigations have demonstrated that macrophages play a crit ical role in the first-line cellular defense mechanism against infecti on with Cryptococcus neoformans. In the present study, to elucidate th e way in which anticryptococcal activity of macrophages is regulated a t the site of infection, pulmonary intraparenchymal macrophages were d irectly analyzed for expression of their surface molecules and their p hagocytic activities against the organism, and the effects of depletio n of T cells and endogenous IFN-gamma in vivo on these parameters were examined. In the lungs of mice intratracheally inoculated with heat-k illed C. neoformans, macrophages mere activated, as indicated by augme nted expression of MHC class II, intercellular adhesion molecule-1 (IC AM-1) and Fc receptor (FcR), and about two-thirds of macrophages were found to have ingested an average of 3.77 +/- 0.12 yeast cells per mac rophage. In mice depleted of both CD4(+) and CD8(+) T cells by injecti ng the specific monoclonal antibodies (mAbs) or anti-IFN-gamma mAb, no t only augmentation of the expression of macrophage activation markers but also phagocytosis of C. neoformans was significantly reduced. The se results suggest that anticryptococcal activity of macrophages is re gulated by IFN-gamma endogenously produced by T cells. Additionally, t reatment with IFN-gamma were shown to significantly prolong the surviv al time of mice infected with viable C. neoformans. Additionally, prei mmunization with heat-killed C. neoformans significantly prolonged the survival time of mice which received the following infection.