Most of our attention is being directed towards obtaining further evidence for our hypothesis that transplantation immunity is major histocompatibility complex (MHC) restricted. Thus, we contend that transplantation antigens are not recognized per se but are only recognized in association with the MHC of the cells that present them to the immune system. We also propose that the direct effect of transplantation antigens on the immune system of the host is to induce tolerance, and that immunity occurs only when these antigens are presented to the host by antigen presenting cells (APC) MHC compatible with the graft. To further explore this situation we are turning our attention to the diabetes that occurs in BB rats. In this regard, attempts are being made to alleviate this hyperglycemic condition in suitably tolerant animals (rendered tolerant at birth by intravenous inoculation of bone marrow cells) with MHC compatible and incompatible islets of Langerhans. These islets are being transplanted under the kidney capsule or are being inoculated intraportally. (CS)

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA018640-16
Application #
3165006
Study Section
Immunobiology Study Section (IMB)
Project Start
1978-07-01
Project End
1986-12-31
Budget Start
1986-01-01
Budget End
1986-12-31
Support Year
16
Fiscal Year
1986
Total Cost
Indirect Cost
Name
University of Pennsylvania
Department
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Desquenne-Clark, L; Kimura, H; Silvers, W K (1993) Ability of bone marrow cells and lymph node cells to induce tolerance of skin in MHC-congenic rats. Transplantation 56:1602-3
Desquenne-Clark, L; Kimura, H; Naji, L et al. (1993) Comparison of the abilities of MHC-compatible bone marrow cells and lymph node cells to induce tolerance of skin allografts in rats. Transplantation 56:1230-3
Davies, J D; Silvers, W K; Wilson, D B (1992) A transplantation antigen, possibly of mitochondrial origin, that elicits rejection of parental strain skin grafts by F1 rats. Transplantation 54:730-1
Desquenne-Clark, L; Kimura, H; Silvers, W K (1992) Priming and cross-priming for H-Y in female mice. Transplantation 54:916-9
Chen, H D; Silvers, W K (1991) Major histocompatibility complex restriction and cross-priming of H-Y antigen in rats. Transplantation 51:259-61
Honda, H; Kimura, H; Silvers, W K et al. (1990) Perivascular location and phenotypic heterogeneity of microglial cells in the rat brain. J Neuroimmunol 29:183-91
Miyamoto, M; Desquenne-Clark, L; Kimura, H et al. (1990) Major histocompatibility complex-unrestricted tolerance induction in rats. Transplantation 49:833-5
Desquenne-Clark, L; Kimura, H; Silvers, W K (1988) The influence of interleukin 2 on the persistence of tolerance. Transplantation 46:774-5
Desquenne-Clark, L; Chen, H D; Silvers, W K (1987) Influence of the major histocompatibility complex (MHC) on the response to and expression of H-Y in rats. Dev Genet 8:189-94
Kimura, H; Silvers, W K; Wilson, D B (1986) Immunogenicity and crossreactivity of specificity-associated markers on alloreactive T cells. Confirmation based on the model of tolerance abolition by adoptive transfer. J Exp Med 163:469-73

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