The IL-12 role in donor cell engraftment in a murine model of semiallogenic GVH disease with signs of autoimmune disease.
We analyzed the IL-12 effect in an autoimmune disease induced in a semiallogenic murine model of graft-vs-host disease (GVHD) Balb/c semiallogenic lymphoid cells i.v. infected in hybrid mice (Balb/c x A/J) F1 (CAF). IL-12 was administered 1 h before cell transplantation following two different protocols: (a) injecting 2 microg of mrIL-12 (murine recombinant IL-12) per mouse before the first semiallogenic cell injection; or (b) injecting the 2 microg of mrIL-12 fractionated in 5 days. ATh1 response was produced but an acute GVHD did not appear although differences in class I and II major histocompatibility complex (MHC) antigens were present. Four days after the semiallogenic cell transfer, IL-12 treated mice showed a marked reduction in the percent of spleen B cells compared with CAF1 control and CAF1 + Balb/c GVHD mice. After 5-6 months of follow-up, the donor cell chimerism increased significantly in spleen (70 +/- 31 vs. 43 +/- 31%) and in thymus. Flow cytometry of spleen lymphocytes demonstrated that donor chimerism was made up of TCD4, TCD8 and B lymphocytes and was higher in animals injected with IL-12. Moreover, CD8 T lymphocytes were 100% donor origin in the IL-12-injected group of GVHD animals and 50% origin in the IL-12-non-injected CAF1 + Balb/c group of animals. This paper shows that: (1) IL- 12 may play a role in the mechanisms of donor cell engraftment, probably produced by a CTL donor anti-host mechanism; (2) no acute GVHD was induced in spite of class I and II MHC differences; (3) IL-12 did not show any effect on the AR-like clinical signs of disease developed in this model of GVHD although histological subclinical signs were less frequent, and no glomerulonephritis was detected in the IL-12-treated GVHD mice.
Department of Immunology, Hospital de Sant Pau, Avgda S. Antoni Ma Claret 167, 08025, Barcelona, Spain.
Francisca
F
Gallego
Carmen
C
Gelpí
D000818:Animals; D001168:Arthritis / Q000276:immunology / Q000378:metabolism; D001323:Autoantibodies / Q000276:immunology; D004195:Disease Models, Animal; D005434:Flow Cytometry; D006086:Graft vs Host Disease / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D018664:Interleukin-12 / Q000276:immunology / Q000378:metabolism*; D007378:Interleukins / Q000276:immunology / Q000378:metabolism; D051379:Mice; D013154:Spleen / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism
D001323:Autoantibodies; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007378:Interleukins; D018664:Interleukin-12