Title
Ifn-gamma prevents th2 cell-mediated pathology after neonatal injection of semiallogenic spleen-cells in miceIfn-gamma prevents th2 cell-mediated pathology after neonatal injection of semiallogenic spleen-cells in mice
Author
Faculty/Department
Faculty of Medicine and Health Sciences
Publication type
article
Publication
Baltimore, Md,
Subject
Human medicine
Source (journal)
The journal of immunology. - Baltimore, Md
Volume/pages
153(1994):6, p. 2361-2368
ISSN
0022-1767
ISI
A1994PF18900001
Carrier
E
Target language
English (eng)
Abstract
BALB/c mice injected at birth with 1O(8) (A/J X BALB/c)F-1 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-lO. As IFN-gamma is known to inhibit the development of TH2 cells, we attempted to modulate HVG disease toy injecting rIFN-gamma. First, we found that 10 pg of rIFN-gamma given on days 1 and 3 after birth reduced the serum hyper-lgE of HVG mice by 90% and the serum hyper-lgGl, 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 lgG1 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 lgs 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.
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