Immunology
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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

Our group is interested in understanding the molecular and cellular elements responsible for self tolerance and prevention of autoimmune disease.

Not all self reactive T cells are deleted in the thymus. We have defined inhibitory interactions between regulatory CD4 and CD8 T cell subsets and immunological effector cells that serve to maintain self tolerance in the face of chronic infectious stimuli (1,3). Recent studies have shown that expression of the MHC class Ib molecule, Qa-1, by CD4+ cells protects them from NK lysis due to an interaction between Qa-1–Qdm and CD94–NKG2A on NK cells (7).

We have also defined a new molecular link in the death pathway that eliminates self-reactive cells in the thymus. Biochemical and genetic studies uncovered the role of a novel serine kinase termed MINK that bridges signals from autoreactive T cell receptors to cellular apoptosis (4).

Failure of intrathymic deletion and regulatory interactions can lead to autoimmune diseases, including Systemic Lupus Erythematosus (SLE). We have defined a gene - Osteopontin (Opn) that, when dysregulated, may play a key role in this pathogenic process. Secreted Opn (Opn-s) is essential for the development of IFN-gamma-producing Th1 cells (5), while intracellular Opn (Opn-i) is essential for expression of Type I IFN by pDC (6). Analysis of mice lacking the Opn gene will test the role of Opn in animal models of SLE, while definition of the Opn response in a test tube may allow identification of small molecules that can inhibit this process.

 

 

Papers & Publications:

  1. Hu D/ Ikizawa K, Lu L, Sanchirico ME, Shinohara ML, Cantor H. 2004.. Analysis of regulatory CD8 cells in mice deficient in the Qa-1 class Ib molecule. Nature Immunology, 5, 516 - 523.
  2. McCarty N, Shinohara ML, Lu L, Cantor H.. 2004. Detailed analysis of gene expression during development of T cell lineages in the thymus. Proc. Natl. Acad. Sci. USA, 101:9339-44.
  3. Paust S, Lu L, McCarty N, Cantor H. 2004. Engagement of B7 on effector T cells by regulatory T cells prevents autoimmune disease. Proc. Natl. Acad. Sci. USA, 101:10398-403.
  4. McCarty N, Paust S, Ikizawa K, Dan I, Li X, Cantor H. 2005. Signaling by MINK plays an essential role in negative selection of autoreactive thymocytes. Nature Immunology, 6:65-72.
  5. Shinohara ML, Jansson M, Hwang ES, Werneck MBF, Glimcher LH, Cantor H. 2005. T-bet dependent expression of Osteopontin contributes to T cell polarization. Proc. Natl. Acad. Sci. USA, 102:17101-17106.
  6. Shinohara ML, Lu L, Bu J, Werneck MBF, Kobayashi KS, Glimcher LH, Cantor H. 2006. Osteopontin expression is essential for IFN-alpha production by plasmacytoid dendritic cells. Nature Immunology, 7, 498 – 506.
  7. Lu L, Ikizawa K, Hu D, Werneck MBF, Wucherpfennig KW, Cantor H. 2007. Regulation of activated CD4+ T cells by NK cells via the Qa-1-NKG2A inhibitory pathway. Immunity, 26:593-604.