Michael Bennett, M.D.

My laboratory is involved in studies of murine bone marrow transplantation (BMT) and natural killer (NK) cells. NK cells, unlike T or B cells, fail to rearrange TCR or Ig receptor genes and, therefore, do not have a vast repertoire of receptors. The receptors recently discovered, however, do recognize and bind to MHC class I molecules. Rather than killing target cells after this recognition event, a "negative signal" is transmitted to the NK cells. A failure to receive the negative signal allows the NK cell to kill through positive signals. We are analyzing these activating receptors and how they regulate the ability of mice to reject bone marrow grafts. In addition, we are developing a model system of treatment of leukemia by blocking the negative signals that NK cells receive from class I molecule; this allows NK cells to lyse autologous tumor cells very well. T cell depletion of marrow grafts prevents severe graft-v-host disease but makes the marrow grafts very sensitive to rejection. Clinically applicable approaches are used to induce 'tolerance' to allogeneic marrow grafts to allow the use of T cell depletion safely.

Medical School

Baylor College of Medicine (1961)

• Bone Marrow Transplantation
• Natural Killer Cells

Featured Publications

Tolerance and aloreactivity of the Ly49D subset of murilne NK cells.

George TC, Ortaldo JR, Lemieux S, Kumar V, Bennett M Journal of Immunology Spring 1999 163 1859-1867

Extended self-renewal capacity of pluripotent hemopoietic cells: Association with persistent Friend focus forming virus.

Echner RJ, Hettrick KL, Greenberger JS, Bennett M Cell Spring 1982 31 731-738

Mechanisms of genetic resistance to Friend virus leukemia in mice. I. Role of 89Sr-sensitive effector cells responsible for rejection of bone marrow allografts.

Kumar V, Echner RJ, Bennett M Joiurnal of Experimental Medicine Summer 1974 139 1093-1109

Peculiar immunobiology of bone marrow allografts I. Graft rejection by heavily irradiated "responder" mice

Cudkowicz G, Bennett M Journal of Experimental Medicine Winter 1971 134 8-102

Peculiar immunobiology of bone marrow allografts. II. Rejection of parental grafts by F1 hybrid mice.

Cudkowicz G, Bennett M Journal of Experimental Medicine Summer 1971 135 1513-1528

NK inhibitory blockade for purging leukemia: effects on hematopoiesis

Koh CY, Raziuddin A, Welniak LA, Blazar BR, Bennett M, Murphy WJ Biology of Blood & Bone Marrow Transplantation Winter 2002 8 17-25

Increased bone marrow allograft rejection by depletion of NK cels expressing inhibitory Ly49 receptors for donor class I antigens

Raziuddin A, Longo DL, Winkler-Pickett R, Bennett M, Ortaldo JR, Murphy WJ Blood Fall 2002 vol 100 3026-3033

Definition of additional ligands for Ly49I(B6) using FVB.Ly49I(B6) transgenic mice and B6 NK cell effectors

Morris MA, Koullich E, Liu J, Arora V, George TC, Schatzle JD, Bennett M Transplantation Fall 2002 74 1449-1454

Perforin- and Fas-dependent mechanisms of natural killer cell-mediated rejection of incompatible bone marrow cell graftsn

Taylor MA, Ward B, Schatzle JD, Bennett M European Journal of Immunology Spring 2002 32 793-799

Rejection of marrow allografts: importance of H2 homozygosity of donor cells.

Bennett M Transplantation Spring 1972 14 289-2998

• Frances Stone Burns
  Best Cancer Research Project in Massachusetts (1973)
• A. J. Gill
  Professor of Pathology 1991-present (0)
• Research Career Development
  National Cancer Institute 1974-1979 CA70879 (0)

• American Association of Immunologists
• International Society of Experimental Hematology