CHRONIC LISTERIA INFECTION IN SCID MICE - REQUIREMENTS FOR THE CARRIER STATE AND THE DUAL ROLE OF T-CELLS IN TRANSFERRING PROTECTION OR SUPPRESSION

Listeriosis in mice with the SCID mutation results in a chronic infect ion, The chronic infection is characterized by abundant granulomas and neutrophil infiltrates, Both lesions were particularly noticeable in the liver, In the liver, about 95% are granulomas with 5% microabscess es involving intrahepatic infection, The majority of Listeria resided in membrane-bound vacuolar structures of the macrophages and not in th e cytosol, Three manipulations resulted in alterations in the equilibr ium between granulomas and liver microabscesses, with massive transfer of the infection to the hepatocyte and dissolution of the granulomas: depletion of neutrophils and neutralization of IFN-gamma and TNF-alph a. We did not find a role for IL-12, IL-10, or nitric oxide, Adoptive transfer studies showed a decisive role for both CD4(+) and CD8(+) T c ells for an effective immune response, i.e., clearance of bacteria, gr anuloma formation with lymphocytes, and disappearance of microabscess. Clearance of Listeria was induced by transfer of CD8(+) T cells from mice with targeted disruption of the IFN-gamma structural gene (IfgTM1 KO), even in the presence of neutralizing mAb to IFN-gamma. In marked contrast, transfer of CD4(+) T cells from IfgTM1KO mice exacerbated th e infection in the chronically infected SCID mice, resulting in increa sed mortality with dissolution of the granulomas and severe hepatic in fection with neutrophil infiltration, Thus, these data indicate that b oth IFN-gamma-dependent and -independent mechanisms are operative in t he context of a chronic listerial infection.