Preliminary data in the applicant's laboratory have led to the hypothesis that the donor lymphoid cells promote engraftment primarily by recognizing and eliminating or inactivating host lymphocytes that otherwise remain capable of causing rejection. Lymphokines produced by alloactivated T cells may play a subsidiary role but are not sufficient to enable durable engraftment if host lymphocytes are not eliminated. The goals of this proposal are to assess whether donor T cells must exhibit specificity for host alloantigens present restrictively on host lymphoid cells or in cells with non-specific cytotoxic activity mediated graft facilitation. The following specific aims are: 1) to determine whether T cells tolerant to host alloantigens or donor T cells with allospecificity can facilitate engraftment; 2) to determine whether NK cells and activated NK cells can facilitate marrow engraftment without causing GVHD; 3) to assess the abilities of CD4 and/or CD8 cell facilitating engraftment across class I or class II MHC barriers; 4) to assess whether lymphoid cells and hematopoietic cells must be recognized by donor cells to permit graft acceptance; and 5) to test whether alloactivated T cells can accelerate engraftment and increase survival when limited numbers of cells are transplanted in recipients where rejection is not a limiting factor.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI027951-03
Application #
3142262
Study Section
Immunobiology Study Section (IMB)
Project Start
1990-08-01
Project End
1994-07-31
Budget Start
1992-08-01
Budget End
1993-07-31
Support Year
3
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Fred Hutchinson Cancer Research Center
Department
Type
DUNS #
075524595
City
Seattle
State
WA
Country
United States
Zip Code
98109