CERTAIN HOST-DONOR RAT STRAIN COMBINATIONS DO NOT REJECT BRAIN ALLOGRAFTS AFTER SYSTEMIC SENSITIZATION

被引:24
作者
ISONO, M [1 ]
POLTORAK, M [1 ]
KULAGA, H [1 ]
ADAMS, AJ [1 ]
FREED, WJ [1 ]
机构
[1] ST ELIZABETH HOSP, NIMH, CTR NEUROSCI, NEUROPSYCHIAT BRANCH, WASHINGTON, DC 20032 USA
关键词
D O I
10.1006/exnr.1993.1106
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
To investigate the factors related to allogenic brain graft rejection, rat cortex from either LEW-RT11 or BN-RT1(n) rats was transplanted into brains of several isogenic and allogenic inbred strains: F344-RT11, LEW-RT11, BN-RT1n, AO-RT1u, PGV-RT1c, PGV-RT1u, and PGV-RT11. Each donor and host combination was subsequently subdivided into two subgroups. One group was systematically sensitized twice with donor skin tissue and another group served as a sham-sensitization control. Four weeks after the second sensitization, host brains were examined histologically, and the percentage volume of each graft that showed increased cellularity was estimated. Expression of major histocompatibility complex (MHC) and T cell antigens was also studied immunocytochemically. Almost all grafts in sham-sensitized animals from all groups were accepted with minimal or no reaction. However, two strains, (AO-RT1u and F344-RT11) showed considerable cell infiltration and expression of MHC antigens even without sensitization. After sensitization, almost all allogenic strain combinations showed greater signs of rejected-related responses. The severity of the tissue reaction, however, varied considerably between groups. All grafts from BN-RT1(n) donors were rejected severely in all host strains. For LEW-RT11 donors, grafts survived well in some host strains (BN-RT1n, AO-RT1u, PGV-RT1c, and PGV-RT1u), even with MHC + non-MHC disparity. Curiously, F344-RT11 hosts rejected LEW-RT11 grafts even though the two strains have the same MHC loci, but different minor histocompatibility (mH) loci. For both donor strains, experimental autoimmune encephalomyelitis-susceptible hosts tended to show more vigorous rejection response. Histological data indicated that CD4+ cells were the predominant infiltrating cell type(s). These cells appeared to be primarily blood-derived macrophages and microglia. Relatively few CD8+ cells were present even in grafts with several immune reactions. Our results suggest that MHC disparity is not the only factor affecting the survival of allogenic neural grafts, with or without systemic sensitization, and in fact plays a relatively limited role. It is suggested that susceptibility to neural graft rejection depends on a number of factors, most importantly haplotype of the donor, but also including Ir gene, host MHC allele, and host susceptibility to autoimmune disease. © 1993 Academic Press. All rights reserved.
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页码:48 / 56
页数:9
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