A TH1 CELL-LINE (3E9.I) FROM RESISTANT A J MICE INHIBITS INDUCTION OFMACROPHAGE PROCOAGULANT ACTIVITY IN-VITRO AND PROTECTS AGAINST MHV-3 MORTALITY IN-VIVO/

Induction of immune coagulants has been implicated in the pathogenesis of murine hepatitis virus strain 3 (MHV-3)-induced fulminant hepatic necrosis. Previous work from our laboratory has shown that the inducti on of procoagulant activity (PCA) correlates with the resistance/susce ptibility to disease in inbred and recombinant inbred (RI) strains of mice. Macrophages from susceptible, but not resistant, strains of mice expressed increased levels of PCA in response to MHV-3 stimulation. T lymphocytes, however, had a marked regulatory role in the final expre ssion of macrophage PCA. CD3(+) CD4(+) CD8(-) lymphocytes from RI H-2 compatible susceptible mice were able to instruct macrophages from sus ceptible mice to express significantly augmented levels of PCA, wherea s CD3(+) lymphocytes from RI H-2 compatible MHV-3-immunized resistant mice were able to suppress induction of PCA. In this present study, T- cell lines were derived from draining popliteal lymph nodes from resis tant A/J mice, which had been immunized with MHV-3. All T-cell lines s howed marked proliferation to MHV-3 and MHV-JHM which was major histoc ompatibility complex (MHC) restricted. All cell lines were CD3(+), fou r of these were CD4(+) and one was CD8(+). All of the CD4(+) cell line s produced IL-2 and two produced interferon-gamma (IFN-gamma), consist ent with the Th1 cytokine profile. One cell line (3E9.1) was able to i nhibit the induction of macrophage PCA through production of a soluble factor although cell-to-cell contact could not be excluded. This CD4( +) T-cell line conferred protection to infected and susceptible AXB8 m ice. These results demonstrate that the existence of a Th1 subpopulati on of cells with a regulatory effect on macrophage PCA induction in MH V-3-infected mice contributes to the resistance of the A/J strain of m ice to MHV-3 infection.