Bone marrow transplantation and natural killer (NK) cells are investigated in this laboratory. NK cells acutely reject incompatible marrow cells. NK cells do not rearrange T or B cell receptor genes, but do have two important receptor "gene families", NKRP1 and Ly-49, coding for Type II integral membrane proteins. The inheritance pattern of specific NK receptor genes appears to control the genetic ability to reject marrow allografts. We have made monoclonal antibodies to some of these receptors and have cloned Ly-49C and Ly-49I genes. Ly-49I transgenic mice have been generated to study the function of one of these genes separated from the two families on chromosome 6. Solid tissue graft antigens (MHC Class I and II) are inherited co-dominantly and thus F1 hybrids always accept solid tissue grafts. NK cell receptors recognize class I antigens, but this leads to ’negative signaling’ for the most part; thus F1 hybrid mice reject parental strain and allogeneic marrow grafts because subsets of their NK cells fail to receive negative signals from donor class I antigens. Nevertheless ’tolerance’ to marrow grafts can be induced, and this laboratory is developing clinically applicable methods to accomplish this as well as determining the mechanism of tolerance. Marrow depleted of T cells to prevent graft-versus-host disease is very susceptible to rejection and we are attempting to characterize ’graft facilitating T cells’ that tend to prevent rejection.
RESEARCH INTERESTS
Bone Marrow Transplantation
Natural Killer Cells
RECENT PUBLICATIONS
Raziuddin A, Longo DL, Winkler-Pickett R, Bennett M, Ortaldo JR, Murphy WJ, "Increased bone marrow allograft rejection by depletion of NK cels expressing inhibitory Ly49 receptors for donor class I antigens" Blood, vol 100:3026-3033, Fall 2002
Taylor MA, Ward B, Schatzle JD, Bennett M, "Perforin- and Fas-dependent mechanisms of natural killer cell-mediated rejection of incompatible bone marrow cell graftsn" European Journal of Immunology, 32:793-799, Spring 2002
Koh CY, Raziuddin A, Welniak LA, Blazar BR, Bennett M, Murphy WJ, "NK inhibitory blockade for purging leukemia: effects on hematopoiesis" Biology of Blood & Bone Marrow Transplantation, 8:17-25, Winter 2002
Morris MA, Koullich E, Liu J, Arora V, George TC, Schatzle JD, Bennett M, "Definition of additional ligands for Ly49I(B6) using FVB.Ly49I(B6) transgenic mice and B6 NK cell effectors" Transplantation, 74:1449-1454, Fall 2002
Bennett M, "Rejection of marrow allografts: importance of H2 homozygosity of donor cells." Transplantation, 14:289-2998, Spring 1972
SIGNIFICANT PUBLICATIONS
Kumar V, Echner RJ, Bennett M, "Mechanisms of genetic resistance to Friend virus leukemia in mice. I. Role of 89Sr-sensitive effector cells responsible for rejection of bone marrow allografts." Joiurnal of Experimental Medicine, 139:1093-1109, Summer 1974
Cudkowicz G, Bennett M, "Peculiar immunobiology of bone marrow allografts. II. Rejection of parental grafts by F1 hybrid mice." Journal of Experimental Medicine, 135:1513-1528, Summer 1971
Cudkowicz G, Bennett M, "Peculiar immunobiology of bone marrow allografts I. Graft rejection by heavily irradiated "responder" mice" Journal of Experimental Medicine, 134:8-102, Winter 1971
Echner RJ, Hettrick KL, Greenberger JS, Bennett M, "Extended self-renewal capacity of pluripotent hemopoietic cells: Association with persistent Friend focus forming virus." Cell, 31:731-738, Spring 1982
George TC, Ortaldo JR, Lemieux S, Kumar V, Bennett M, "Tolerance and aloreactivity of the Ly49D subset of murilne NK cells." Journal of Immunology, 163:1859-1867, Spring 1999
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