Samuel M. Behar

Division of Rheumatology, Immunology and Allergy
Brigham and Women's Hospital
Smith Bldg., Room 516B
One Jimmy Fund Way
Boston, MA 02115
Tel: 617-525-1033
Fax: 617-525-1010
email:sbehar@rics.bwh.harvard.edu
Webpage: The Behar Lab Page
4 postdoctoral fellows, 2 graduate students, 2 research assistants

Immunity to Tuberculosis. It is estimated that 1/3 of the world’s population has been infected with Mycobacterium tuberculosis (Mtb). In the majority of infected people, the immune response is able to adequately control the infection, and consequently only 5-10% will develop clinical disease during their lifetime. My long-term goal is to understand the immunological basis for protective immunity. One way we are investigating this problem is to determine why different mouse strains differ in their susceptibility to tuberculosis. We have observed that certain susceptible mouse strains are unable to efficiently recruit T cells to the lung following infection with Mtb, and this failure likely contributes to increased mortality and morbidity of susceptible mice. Therefore, we are particularly interested in the early events leading to the initiation of the pulmonary immune response following respiratory Mtb infection. This includes establishing how T cells and myeloid cells are recruited back to the lung and how these cells mediate their effector functions.

Although BCG is used universally as a vaccine, its efficacy in preventing pulmonary tuberculosis is controversial. Most Mtb infected individuals develop long-lived immunity that contains the infection in a T cell-dependent manner. Thus, there is considerable interest in how different T cell subsets contribute to immunity and whether vaccination can stimulate protective T cells. Delineating the role of CD8+ T cells in host immunity to Mtb has been hindered by the paucity of antigens known to be recognized by CD8+ T cells. Our antigen discovery program has successfully identified and defined several mycobacterial peptide epitopes that are recognized by CD8+ T cells. For example, CD8+ T cells specific for culture filtrate protein-10 (CFP10) are found in infected people, indicating that CFP10 can prime CD8+ T cells after infection. Notably, CFP10 is encoded in the RD1 genetic locus, which is associated with Mtb virulence. The aim of our studies is to identify, enumerate and functionally characterize antigen-specific CD8+ T cells that are elicited following pulmonary infection. Finally, we are determining whether these antigens can be used as vaccines to elicit protective immunity.

Finally, we are also interested in the role of CD1d restricted NKT cells in microbial immunity. The CD1d protein is a member of the CD1 family of β2 microglobulin-associated proteins. In contrast to class I and II MHC molecules, CD1 proteins have evolved to present lipid and glycolipid molecules to T cells. While CD1a, -b, and –c (group I CD1 proteins) have been shown to present foreign microbial antigens to human αβTCR+ T cells, CD1d-restricted T cells have been implicated in immunoregulation, and may be involved in microbial immunity, both in human disease and in mouse models. Our ultimate goal is to understand how the immune system contains Mtb and why impairment of cell mediated immunity leads to reactivation of tuberculous disease.

Papers & Publications:

1. Kamath AB, Woodworth J, Xiong X, Behar SM. CD8+ T cells recognizing culture filtrate protein-10 (CFP10) are generated following Mycobacterium tuberculosis infection and are cytolytic in vivo. J. Exp. Med. 2004; 200:1479-1489.
2. Skold M, Xiong X, Illarionov PA, Besra GS, Behar SM. Regulation of CD1d by proinflammatory signals mediates NKT cell activation. J. Immunol. 2005, 175: 3584-3593.
3. Woodworth J, Behar SM. Mycobacterium Tuberculosis specific CD8+ T cells and their role in immunity. 2006. Critical Reviews in Immunology; 26:317-352
4. Kamath AB, Woodworth J, Behar SM. Antigen-specific CD8+ T cells and the development of central memory during Mycobacterium tuberculosis infection. 2006; J. Immunol.177:6361-9.
5. Behar SM, Porcelli SA. CD1-Restricted T Cells in Host Defense to Infectious Diseases. In T Cell Activation by CD1 and Lipid Antigens. 2007; Current Topics in Microbiology and Immunology, Vol 314: 215-250.