C SUBREGION FACTOR SUPPRESSES LYMPttOKINE

The spontaneous modula t ion of granulomatous inf lammation in chronic murine schistosomiasis represents a natural ly occurr ing immune process that leads to diminished T cell-mediated inf lammatory responses a round parasite ova in the tissues (14). A recent series of studies has shown that this spontaneous modula t ion is associated with the appearance o f regulatory T cells (5-11) that can adoptively suppress granuloma formation in vivo and lymphokine product ion in vitro (5, 6). One populat ion was active in the long-term adopt ive suppression of acutely infected recipients and expressed the Lyt l+ ,2,3, Ia + phenotype (6, 9), and another caused short-term suppression of responses in uninfected recipients and was defined as Lyt1-,2 +, 3 + (11). Because lymphoeytes of mice undergoing modula t ion had an impaired capaci ty to produce migrat ion inhibition factor (MIF) 1 and eosinophil st imulation promoter (ESP) -active lymphokines (3, 4) that are presumed to function in the formation of the granuloma (12-14), we postulated that modula t ion of the granulomatous response is carried out by regulatory suppressor T (Ts) cells that suppress lymphokine product ion by lymphokine secretor T (TDH) cells. This postulate was confirmed by demonstra t ing that spleens of chronically infected mice contained Lyt1-,2+,3 +, I -J+/I -C + Ts cells that suppress in ~,itro M I F product ion by Lytl+,2,3 -, I a TDH cells of acutely infected animals (8). The present study was undertaken to further examine mechanisms by which inf lammatory and suppressor T cell subpopulat ions interact in the modula t ion o f granuloma formation. We specifically wished to examine the mechanism(s) by which Lyt-l,2+,3 + Ts cells suppress the product ion o f MIF. O u r results suggest that