INTERLEUKIN-12 PREVENTS SEVERE ACUTE GRAFT-VERSUS-HOST DISEASE (GVHD)AND GVHD-ASSOCIATED IMMUNE DYSFUNCTION IN A FULLY MAJOR HISTOCOMPATIBILITY COMPLEX HAPLOTYPE-MISMATCHED MURINE BONE-MARROW TRANSPLANTATION MODEL
Yg. Yang et al., INTERLEUKIN-12 PREVENTS SEVERE ACUTE GRAFT-VERSUS-HOST DISEASE (GVHD)AND GVHD-ASSOCIATED IMMUNE DYSFUNCTION IN A FULLY MAJOR HISTOCOMPATIBILITY COMPLEX HAPLOTYPE-MISMATCHED MURINE BONE-MARROW TRANSPLANTATION MODEL, Transplantation, 64(9), 1997, pp. 1343-1352
Background, We have recently reported that interleukin (IL)-12 prevent
s acute graft-versus-host disease (GVHD)-induced mortality in a full m
ajor histocompatibility complex-plus multiple minor antigen-mismatched
A/J-->B10 bone marrow transplantation (BMT) model, Because most patie
nts have access to a haploidentical, one haplotype-mismatched donor, w
e have now investigated the protective effect of IL-12 against GVHD an
d GVHD-associated immune dysfunction in a haploidentical CBD2F1 (H2(kx
d)) --> B6D2F1 (H2(bxd)) strain combination, Methods. GVHD was induced
by injecting CBD2F1 marrow and spleen cells into lethally irradiated
B6D2F1 mice, Results, In untreated control mice, GVHD resulted in 87%
mortality by day 8 after BRIT, with no survivors beyond day 17. Treatm
ent with a single injection of IL-12 on the day of BMT led to 87% long
-term survival, with no significant weight loss, diarrhea or GVHD skin
changes, The majority of T cells recovering: in these mice showed the
CD62L(+), CD4(low), CD45RB(high) naive phenotype, These T cells showe
d specific tolerance to both host and donor histocompatibility antigen
s, but normal anti-third party (H2(s)) alloresponses in vitro., B-cell
proliferative responses to lipopolysaccharide were also normal in IL-
12-protected mice, Moreover, normal negative selection of thymocytes b
earing T cell receptors with V beta that recognize endogenous superant
igens was observed among CD4(+)CD8(-) thymocytes, indicating a lack of
GVHD-associated thymic selection abnormalities in IL-18-protected all
ogeneic BMT recipients, Conclusions, IL-12 provides permanent protecti
on against an otherwise severe, rapidly lethal GVHD, with no clinical
manifestations of chronic GVHD, immunosuppression or autoimmune featur
es, in a full major histocompatibilty complex haplotype-mismatched mur
ine BMT model.