Harvey Cantor

Baruj Benacerraf Professor of Pathology
Chairman, Department of Cancer Immunology & AIDS

Dana-Farber Cancer Institute
1 Jimmy Fund Way
Smith Building, Room 722
Boston, MA 02115
Tel: 617-632-3348
Fax: 617-632-4630
email:Harvey_Cantor@DFCI.harvard.edu
8-12 Postdoctoral Fellows, 2 Graduate Students

The focus of the lab is on the development and function of T cell subsets. Our studies of their initial development in the thymus have defined a new kinase (MINK) that is activated after engagement of the TCR and self peptides that initiates a pathway culminating in cellular apoptosis (negative selection)(1). These studies have also defined a quality control mechanism that eliminates T cells that have escaped negative selection through fas-dependent apoptosis in peripheral lymphoid tissues.

Studies of the differentiation of T-helper cells have defined an interaction between dendritic cells and T cells that regulates the development of Th1 cells and Th17 cells (2-4). Elaboration of the cytokines Osteopontin and IFNa promotes the Th1 response and suppresses the Th17 response, establishing the pattern of T-helper cell differentiation displayed during the large majority of immune responses.

Studies of the interaction between the MHC class Ib molecular known as Qa-1 in animals and HLA-E in man have revealed its role as a biological target of CD8+ regulatory T cells (5). Several features of Qa-1/HLA-E suggest it will be a particularly potent therapeutic target. For example, blockade or mutation of Qa-1 in animal models uncovers vigorous immune responses that can be mobilized against potential tumor antigens.

More recent studies have shown that NK cells also contribute to the control of adaptive immune responses and that this pathway is also regulated by Qa-1 (6). These studies have extended the functional reach of the NK system to include regulation of adaptive T cell responses and suggest a new clinical strategy for elimination of antigen-activated T cells in the context of transplantation and autoimmunity.

Papers & Publications:

1. McCarty,N., Paust,S., Ikizawa,K., Dan,I., Li,X. & Cantor,H. Signaling by the kinase MINK is essential in the negative selection of autoreactive thymocytes. Nat Immunol 6, 65-72 (2005).

2. Shinohara,M.L., Jansson,M., Hwang,E.S., Werneck,M.B.F., Glimcher,L.H. & Cantor,H. T-bet-dependent expression of osteopontin contributes to T cell polarization. Proc Natl Acad Sci U S A 102, 17101-17106 (2005).

3. Shinohara,M.L., Lu,L., Bu,J., Werneck,M.B.F., Kobayashi,K., Glimcher,L.H. & Cantor,H. Osteopontin expression is essential for IFN-α production by plasmacytoid dendritic cells. Nat. Immunol. 7, 498-506 (2006).

4. Shinohara,M.L., Kim,J.-H., Garcia,V.A. & Cantor,H. Engagement of the Type-I interferon receptor on dendritic cells inhibits promotion of Th17 cells: Role of intracellular Osteopontin. Immunity 29, 68-78 (2008).

5. Hu,D., Ikizawa,K., Lu,L., Sanchirico,M.E., Shinohara,M.L. & Cantor,H. Analysis of regulatory CD8 T cells in Qa-1-deficient mice. Nat Immunol 5, 516-523 (2004).

6. Lu,L., Ikizawa,K., Hu,D., Werneck,M.B.F., Wucherpfennig,K.W. & Cantor,H. Regulation of activated CD4+ T cells by NK cells via the Qa-1-NKG2A pathway. Immunity 26, 593-604 (2007).