DIFFERENTIAL REGULATION OF LA EXPRESSION AND ANTIGEN PRESENTATION BY LISTERIOLYSIN-PRODUCING VERSUS NONPRODUCING STRAINS OF LISTERIA-MONOCYTOGENES

Listeria monocytogenes is an intracellular bacterial pathogen, A singl e gene product, listeriolysin (LLO), is critical for the induction of protective immunity, We now show that listeria that produce functional LLO augment Ia expression by macrophages and are better presented to a Th1, CD4(+) anti-listeria T cell line, We used two genetically engin eered strains of listeria which differed only in their ability (Ly(+)) or inability (Ly(-)) to produce functional LLO. Ia-negative murine ma crophages ingested either Ly(+) or Ly(-), and then were stimulated by interferon-gamma (IFN-gamma), Increasing numbers of live Ly(+), but no t Ly(-), augmented IFN-gamma-induced Ia expression, Ly + by itself did not induce Ia expression, Heat-killed Ly(+) and Ly(-) did not augment IFN-gamma-induced Ia expression, The abundance of Ia on the macrophag e cell surface is one major determinant of antigen presentation to CD4 (+) T cells, Consistent with their ability to augment Ia expression, L y(+) were better presented than Ly(-) to a CD4(+), Th1, anti-listeria T cell line, When macrophages and T cells were from different inbred m ouse strains, antigen presentation required identity at the Class II r egion of the MHC gene complex, This indicated that antigen presentatio n occurred via Is molecules, The increased ability of macrophages to p resent Ly(+) is a product of the macrophage-listeria interaction, not a property of the T cell line 86, If Ia-negative macrophages ingested Listeria and were then stimulated by IFN-gamma, Ly(+) was presented mo re efficiently than Ly(-). On the other hand, if Ia-positive macrophag es ingested Listeria, then Ly(+) and Ly(-) were presented equally well to T cells, Altogether our data is consistent with the hypothesis tha t macrophages interact differently with Ly(+), and that this contribut es to the ability of only live Ly(+) to induce protective immunity.