T-CELL-MACROPHAGE COGNATE INTERACTION IN THE ACTIVATION OF MACROPHAGEEFFECTOR FUNCTION BY TH2 CELLS

The in vitro induction of cytostatic/cytotoxic activity in macrophages generated in spleen cell cultures requires a signal cascade initiated by costimulation with both LPS and IFN-gamma. Th2 lymphocytes, althou gh they do not produce IFN-gamma, can provide the signals necessary fo r induction of cytostatic activity in IFN-gamma-primed macrophages. Th ese signals appear to be delivered by cognate interaction between the Th2 cells and macrophages in that: 1) they are not delivered by cultur e supernatants of Th2 cells activated 6 or 20 h by Con A or by immobil ized anti-CD3 mAb; 2) they are not delivered if cell contact between T h2 cells and macrophages is prevented; and 3) they can be delivered by paraformaldehyde-fixed activated Th2 cells. Paraformaldehyde-fixed re sting Th2 cells cannot stimulate activation of IFN-gamma-primed macrop hages. The Th2 cells must be activated at least 3 h before fixation to acquire macrophage stimulatory activity. Optimal macrophage-stimulati ng activity is attained after 6-h activation of the Th2 and declines t hereafter. Although the activation of IFN-gamma-primed macrophages by viable resting Th2 displays Ag specificity and MHC restriction, the ac tivation of IFN-gamma-primed macrophages by paraformaldehyde-fixed act ivated Th2 is neither Ag specific nor MHC restricted. These observatio ns suggest that T cell-mediated activation of macrophages can involve a signaling cascade of Ag-specific and Ag-nonspecific adhesion events comparable to those hypothesized to occur in T cell-mediated B cell ac tivation.