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FRISC: The Faculty Research Interests Science Comparator |
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Professor of Pathology
Immunology
Molecular
Microbiology
Office: 214-648-4103
FAX: 214-648-4033
Email: bennett.michael@pathology.swmed.edu
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.
Selected Publications:
George T, Mason LH, Ortaldo JR, Kumar V, Bennett M (1999)
Positive recognition of MHC class I molecules by the Ly49D receptor of murine natural
killer cells. J Immunol 162:2035-2043
Schatzle JD, Sheu S, Stepp SE, Mathew PA, Bennett M, Kumar
V (1999) Characterization of inhibitory and stimulatory forms of the murine natural killer
cell receptor 2B4. Proc Natl Acad Sci USA 96:3670-3675
Sivakumar PV, Gunturi A, Salcedo M, Schatzle JD, Lai WC,
Kurepa Z, Pitcher L, Seaman M, Bennett M, Forman J, Kumar V (1999) Expression of
functional CD94/NKG2A inhibitory receptors on fetal NK1.1+Ly49- cells - a possible
mechanism of tolerance during NK cell developoment. J Immunol 162:6976-6980
George T, Yu YYL, Liu J, Davenport C, Lemieux S, Stoneman
ER, Mathew PA, Kumar V, Bennett M 1997 Allorecognition by murine natural killer cells:
Lysis of T lymphoblasts and rejection of bone marrow grafts. Immunol Rev 155:29-40
Davenport C, George T, Devora GA, Morris MA, Gorden BE,
Kumar V, Bennett M (1997) Facilitation of parental-strain marrow engraftment by T cells of
neonatally tolerant mice. Biol Blood Marrow Transplant 3:294-303
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