Wajahat Z. Mehal, M.D., D.Phil.

Assistant Professor
Section of Digestive Diseases and Immunobiology
more on this physician

Research Interests

Antigens presented in the liver often generate a suboptimal immune response that results in their chronic persistence (immune tolerance). This occurs clinically with tolerance to food antigens, to allo-antigens after liver transplantation, and to viral antigens during chronic infection with hepatitis viruses B and C. Despite these long-standing observations, the immune cells in the normal liver were only recently examined in detail. Over the last five years it has been shown that the normal mouse and human liver contains a large number of T cells (between 2-4 x 10⁶ per gram of tissue). In this population conventional CD8+ T cells, and cells with features of natural killer cells and T cells (NK-T cells) are over-represented. The CD8+ T cells have an activated phenotype, are undergoing cell cycle and apoptosis.

My interests are in defining the interactions that occur between the healthy liver and the immune system during immune homeostasis, acute viral infections, and presentation of alloantigens. We have recently shown that the healthy liver retains activated CD8+ T cells flowing through it. This retention is mediated mostly by hepatic ICAM-1 on Kupffer cells, and a proportion of the retained CD8+ T cells are undergoing apoptosis in the liver. Current work is focusing on the fate of activated CD8+ T cells when specific peptide is present in the liver, and also the ability of the liver to prime naive CD8+ T cells.

Figure Legend:
(A) Co-localization of activated CD8+ T cells (green) and Kupffer cells (red) in a mouse liver 30 min. after portal vein injection.

(B) Confocal microscopy of the mouse liver showing apoptosis of portal vein injected activated CD8+ T cells. CD8+ T cells were labeled with a non-specific membrane marker (CFSE: green) and a fluorochrome which signals mitochondrial membrane potential (Mito-tracker red). Viable cells are positive for CFSE and Mitotracker-red (both combine to give a yellow color) and apoptosing cells have lost the Mito-tracker signal and are only CFSE positive (green).

Selected Publications

• Crispe, I.N., and Mehal, W.Z. (1996) Strange brew: T cells in the liver. Immunology Today 17: 522-525.
• Mehal, W.Z., and Crispe I.N. (1998) TCR ligation on CD8+ T cells creates double-negative cells in vivo. J. Immunol. 161: 1686-1693.
• Dao, T., Mehal, W.Z., and Crispe, I.N. IL-18 augments perforin-dependent cytotoxicity of liver NK-T cells. J. Immunol. 161: 2217-2222.
• Mehal, W.Z., Juedes, A.E., and Crispe, I.N. (1999) Selective retention of activated CD8+ T cells by the normal liver. J. Immunol. 163: 3202-3210.
• Mehal, WZ. (1999) T cells in Primary Sclerosing Cholangitis and Autoimmune Hepatitis. In T Cells in the Liver. Editor: Crispe I.N.C. Wiley Publishers.
• Mehal, W.Z., Azzaroli, F., and Crispe, I.N. (2001) Antigen presentation by liver cells controls intrahepatic T cell trapping, whereas bone marrow-derived cells preferentially promote intrahepatic T cell apoptosis. J. Immunol. 167: 667-673.
• Mehal, W.Z., Azzaroli, F., and Crispe, I.N. (2001) Immunology of the healthy liver; old questions and new insights. Gastroenterology 120: 250-260.

Contact

Campus Address
Department of Internal Medicine
333 Cedar Street (LMP 1080)
New Haven, CT 06520

E-mail
wajahat.mehal@yale.edu

Office Phone
(203) 785-3411