CURRENT RESEARCH INTERESTS
T cell activation and costimulatory pathways: role in autoimmunity and tumor responses
RESEARCH DESCRIPTION
Dr. Latchman’s laboratory is interested in investigating the role of costimulatory pathways in autoimmunity and tumor immunity. T cells require two signals from the antigen presenting cells (APC) to become fully functional. The first signal is the antigen provided by the APC and the second is through a group of molecules called costimulators. Costimulatory pathways contribute signals that are critical for both stimulating and inhibiting T cell activation. Three major families provide costimulation: the B7:CD28 superfamily, a TNF:TNFR subfamily that lack death domains, and the CD2 superfamily. There are currently two areas of research in the laboratory. Firstly, we are investigating the function of the CD2:CD48 and CD244:CD48 costimulatory pathways. Utilizing mouse models, the role of CD48 in T, B and NK function is being delineated. Our recent studies have implied an obligatory role for CD48 in tolerance and therefore we are studying how this pathway participates in the development of autoimmune diseases such as systemic lupus erythematosus (SLE). Secondly, we are analyzing the negative regulatory role of the PD-L:PD-1 pathway. PD-1 ligands (PD-L1 and PD-L2) are expressed on freshly isolated carcinomas of the cervix, colon, larynx, lung and breast. The expression of PD- ligands on tumors suggests a potential mechanism by which tumors may evade an immunological response. We are using PD-1 ligand knockout mice to study the effect of these molecules in the induction and eradication of tumors. Our studies suggest that blockade of the interaction of PD-1 ligands and their receptor PD-1 may provide a means to enhance anti-tumor immunity.
SELECTED PUBLICATIONS
Latchman YE and Reiser H: Engagement of murine CD2 by its ligand CD48 leads to enhanced CD4 T cell responses.
Eur. J. Immunol. 1998; 28:4325-4331.
Latchman YE, McKay PF and Reiser H: Identification of the 2B4 molecule as a counter-receptor for CD48.
J. Immunol. (Cutting Edge) 1998; 161:5809-5812
Latchman YE, Wood CR, Chernova T, Chaudhary D, Borde M, Chernova I, Iwai Y, Long AJ, Brown JA, Nunes J, Greenfield EA, Bourque K, Boussiotis VA, Carter LL, Carreno B, Malenkovich N, Nishimura H, Okazaki T, Honjo T, Sharpe AH, and Freeman GJ. PDL2 is a second ligand for PD1 and inhibits T cell activation.
Nat. Immunol. 2001; 2: 261-268.
Liang SC, Latchman YE, Buhlmann JE, Tomczak MF, Horwitz BH, Freeman GJ and Sharpe AH. Regulation and comparison of PD-1, PD-L1, and PD-L2 expression.
Eur. J. Immunol. 2003; 33:2706-2716.
Latchman YE, Liang SC , Wu Y, Chernova T, Sobel RA, Kleem M, Kuchroo VJ, Freeman GJ, and Sharpe AH. PD-L1 deficient mice show that PD-L1 on T cells, APC and host tissues negatively regulates T cells.
PNAS (Track II). PNAS 2004; 101:10691-10696.
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