IFN-gamma prevents Th2 cell-mediated pathology after neonatal injection of semiallogenic spleen cells in mice.
BALB/c mice injected at birth with 10(8) (A/J X BALB/c)F1 hybrid spleen cells develop an autoimmune host-vs-graft (HVG) disease as a result of activation of donor B cells by host CD4+ cells. The antidonor CD4+ cells seem to be Th2-like cells, inasmuch as they are profoundly deficient in IL-2 and IFN-gamma production, but secrete high levels of IL-4 and IL-10. As IFN-gamma is known to inhibit the development of TH2 cells, we attempted to modulate HVG disease by injecting rIFN-gamma. First, we found that 10 micrograms of rIFN-gamma given on days 1 and 3 after birth reduced the serum hyper-IgE of HVG mice by 90% and the serum hyper-IgG1, by 70%. In addition, rIFN-gamma administration significantly decreased the anti-DNA IgG1 titers and prevented the occurrence of anti-glomerular basement membrane and anti-laminin IgG1 Abs as well as the formation of immune deposits in renal glomeruli. These effects were not caused by the abrogation of chimerism, as indicated by the persistence of donor-type B cells in lymph nodes and of Igs bearing donor allotype in serum. MLC experiments indicated that the major effect of early rIFN-gamma administration was to restore the production of IL-2 and IFN-gamma by donor-specific T cells while these cells still secreted significant amounts of IL-4 and IL-10. Unresponsiveness of antidonor cytolytic T cells was not influenced by rIFN-gamma. We conclude that rIFN-gamma prevents the TH2-type response induced by the neonatal injection of semiallogeneic spleen cells and the associated pathology.
Donckier
V
V
Interdisciplinary Laboratory of Experimental Biomedical Research Free University of Brussels, Belgium.
Abramowicz
D
D
Bruyns
C
C
Florquin
S
S
Vanderhaeghen
M L
ML
Amraoui
Z
Z
Dubois
C
C
Vandenabeele
P
P
Goldman
M
M
D000818:Animals; D000831:Animals, Newborn; D000974:Antibodies, Antinuclear / Q000096:biosynthesis; D003601:Cytotoxicity Tests, Immunologic; D006789:Host vs Graft Reaction / Q000276:immunology; D007132:Immunoglobulin Isotypes / Q000096:biosynthesis; D007371:Interferon-gamma / Q000276:immunology*; D007674:Kidney Diseases / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D017710:Lymphocyte Transfusion; D008222:Lymphokines / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000166:cytology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D018183:Transplantation Chimera / Q000276:immunology; D014184:Transplantation, Homologous / Q000276:immunology
D000974:Antibodies, Antinuclear; D007132:Immunoglobulin Isotypes; D008222:Lymphokines; D007371:Interferon-gamma