A Th1 cell line (3E9.1) from resistant A/J mice inhibits induction of macrophage 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 induction of procoagulant activity (PCA) correlates with the resistance/susceptibility 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 expression of macrophage PCA. CD3+ CD4+ CD8- lymphocytes from RI H-2 compatible susceptible mice were able to instruct macrophages from susceptible mice to express significantly augmented levels of PCA, whereas 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 resistant A/J mice, which had been immunized with MHV-3. All T-cell lines showed marked proliferation to MHV-3 and MHV-JHM which was major histocompatibility complex (MHC) restricted. All cell lines were CD3+, four of these were CD4+ and one was CD8+. All of the CD4+ cell lines produced IL-2 and two produced interferon-gamma (IFN-gamma), consistent with the Th1 cytokine profile. One cell line (3E9.1) was able to inhibit 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 mice. These results demonstrate that the existence of a Th1 subpopulation of cells with a regulatory effect on macrophage PCA induction in MHV-3-infected mice contributes to the resistance of the A/J strain of mice to MHV-3 infection.
University of Toronto, Canada.
S
S
Chung
R
R
Gorczynski
B
B
Cruz
R
R
Fingerote
E
E
Skamene
S
S
Perlman
J
J
Leibowitz
L
L
Fung
M
M
Flowers
G
G
Levy
D000818:Animals; D001483:Base Sequence; D001777:Blood Coagulation; D002460:Cell Line; D018352:Coronavirus Infections / Q000276:immunology*; D017931:DNA Primers; D004198:Disease Susceptibility; D006524:Hepatitis, Viral, Animal / Q000276:immunology*; D007113:Immunity, Innate; D008262:Macrophage Activation / Q000276:immunology*; D008264:Macrophages / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D006517:Murine hepatitis virus / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*
D017931:DNA Primers