HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Mehal, W. Z. Articles by Crispe, I. N. Search for Related Content PubMed PubMed Citation Articles by Mehal, W. Z. Articles by Crispe, I. N.

Antigen Presentation by Liver Cells Controls Intrahepatic T Cell Trapping, Whereas Bone Marrow-Derived Cells Preferentially Promote Intrahepatic T Cell Apoptosis¹

Wajahat Z. Mehal^*,, Francesco Azzaroli and I. Nicholas Crispe^2,*

Sections of ^* Immunobiology and Digestive Diseases, Yale University School of Medicine, New Haven, CT 06510

Systemic activation and proliferation of CD8⁺ T cells result in T cell accumulation in the liver, associated with T cell apoptosis and liver injury. However, the role of Ag and APC in such accumulation is not clear. Bone marrow chimeras were constructed to allow Ag presentation in all tissues or alternatively to restrict presentation to either bone marrow-derived or non-bone marrow-derived cells. OVA-specific CD8⁺ T cells were introduced by adoptive transfer and then activated using peptide, which resulted in clonal expansion followed by deletion. Ag presentation by liver non-bone marrow-derived cells was responsible for most of the accumulation of activated CD8⁺ T cells. In contrast, Ag presentation by bone marrow-derived cells resulted in less accumulation of T cells in the liver, but a higher frequency of apoptotic cells within the intrahepatic T cell population. In unmodified TCR-transgenic mice, Ag-induced T cell deletion and intrahepatic accumulation of CD8⁺ T cells result in hepatocyte damage, with the release of aminotransaminases. Our experiments show that such liver injury may occur in the absence of Ag presentation by the hepatocytes themselves, arguing for an indirect mechanism of liver damage.

This article has been cited by other articles:

				D. Moonka, K. A. Milkovich, B. Rodriguez, M. Abouljoud, M. M. Lederman, and D. D. Anthony Hepatitis C Virus-Specific T-Cell Gamma Interferon and Proliferative Responses Are More Common in Perihepatic Lymph Nodes than in Peripheral Blood or Liver J. Virol., December 1, 2008; 82(23): 11742 - 11748. [Abstract] [Full Text] [PDF]

				C. S. Guy, P. M. Mulrooney-Cousins, N. D. Churchill, and T. I. Michalak Intrahepatic Expression of Genes Affiliated with Innate and Adaptive Immune Responses Immediately after Invasion and during Acute Infection with Woodchuck Hepadnavirus J. Virol., September 1, 2008; 82(17): 8579 - 8591. [Abstract] [Full Text] [PDF]

				I. Klein, J. C. Cornejo, N. K. Polakos, B. John, S. A. Wuensch, D. J. Topham, R. H. Pierce, and I. N. Crispe Kupffer cell heterogeneity: functional properties of bone marrow derived and sessile hepatic macrophages Blood, December 1, 2007; 110(12): 4077 - 4085. [Abstract] [Full Text] [PDF]

				R. Safadi, E. Zigmond, O. Pappo, Z. Shalev, and Y. Ilan Amelioration of hepatic fibrosis via beta-glucosylceramide-mediated immune modulation is associated with altered CD8 and NKT lymphocyte distribution Int. Immunol., August 13, 2007; (2007) dxm069v1. [Abstract] [Full Text] [PDF]

				R. T. Robinson and J. D. Gorham TGF-beta1 Regulates Antigen-Specific CD4+ T Cell Responses in the Periphery J. Immunol., July 1, 2007; 179(1): 71 - 79. [Abstract] [Full Text] [PDF]

				N. K. Polakos, I. Klein, M. V. Richter, D. M. Zaiss, M. Giannandrea, I. N. Crispe, and D. J. Topham Early Intrahepatic Accumulation of CD8+ T Cells Provides a Source of Effectors for Nonhepatic Immune Responses J. Immunol., July 1, 2007; 179(1): 201 - 210. [Abstract] [Full Text] [PDF]

				J. Morimoto, X. Tan, R. M. Teague, C. Ohlen, and P. D. Greenberg Induction of Tolerance in CD8+ T Cells to a Transgenic Autoantigen Expressed in the Liver Does Not Require Cross-Presentation J. Immunol., June 1, 2007; 178(11): 6849 - 6860. [Abstract] [Full Text] [PDF]

				R. Keating, W. Yue, J. A. Rutigliano, J. So, E. Olivas, P. G. Thomas, and P. C. Doherty Virus-Specific CD8+ T Cells in the Liver: Armed and Ready to Kill J. Immunol., March 1, 2007; 178(5): 2737 - 2745. [Abstract] [Full Text] [PDF]

				A. Horani, N. Muhanna, O. Pappo, A. Melhem, C. E. Alvarez, S. Doron, W. Wehbi, K. Dimitrios, S. L. Friedman, and R. Safadi Beneficial effect of glatiramer acetate (Copaxone) on immune modulation of experimental hepatic fibrosis Am J Physiol Gastrointest Liver Physiol, February 1, 2007; 292(2): G628 - G638. [Abstract] [Full Text] [PDF]

				F. Isayama, I. N. Hines, M. Kremer, R. J. Milton, C. L. Byrd, A. W. Perry, S. E. McKim, C. Parsons, R. A. Rippe, and M. D. Wheeler LPS signaling enhances hepatic fibrogenesis caused by experimental cholestasis in mice Am J Physiol Gastrointest Liver Physiol, June 1, 2006; 290(6): G1318 - G1328. [Abstract] [Full Text] [PDF]

				N. K. Polakos, J. C. Cornejo, D. A. Murray, K. O. Wright, J. J. Treanor, I. N. Crispe, D. J. Topham, and R. H. Pierce Kupffer Cell-Dependent Hepatitis Occurs during Influenza Infection Am. J. Pathol., April 1, 2006; 168(4): 1169 - 1178. [Abstract] [Full Text] [PDF]

				I. Klein and I. N. Crispe Complete differentiation of CD8+ T cells activated locally within the transplanted liver J. Exp. Med., February 21, 2006; 203(2): 437 - 447. [Abstract] [Full Text] [PDF]

				J. Sun, B. Tumurbaatar, J. Jia, H. Diao, F. Bodola, S. M. Lemon, W. Tang, D. G. Bowen, G. W. McCaughan, P. Bertolino, et al. Parenchymal Expression of CD86/B7.2 Contributes to Hepatitis C Virus-Related Liver Injury J. Virol., August 15, 2005; 79(16): 10730 - 10739. [Abstract] [Full Text] [PDF]

				W. Z. Mehal, S. Z. Sheikh, L. Gorelik, and R. A. Flavell TGF-{beta} signaling regulates CD8+ T cell responses to high- and low-affinity TCR interactions Int. Immunol., May 1, 2005; 17(5): 531 - 538. [Abstract] [Full Text] [PDF]

				D. A. Murray and I. N. Crispe TNF-{alpha} Controls Intrahepatic T Cell Apoptosis and Peripheral T Cell Numbers J. Immunol., August 15, 2004; 173(4): 2402 - 2409. [Abstract] [Full Text] [PDF]

				C. A. Wysocki, S. B. Burkett, A. Panoskaltsis-Mortari, S. L. Kirby, A. D. Luster, K. McKinnon, B. R. Blazar, and J. S. Serody Differential Roles for CCR5 Expression on Donor T Cells during Graft-versus-Host Disease Based on Pretransplant Conditioning J. Immunol., July 15, 2004; 173(2): 845 - 854. [Abstract] [Full Text] [PDF]

				Q. Cao, Y. Xia, M. Azadniv, and I. N. Crispe The E2F-1 Transcription Factor Promotes Caspase-8 and Bid Expression, and Enhances Fas Signaling in T Cells J. Immunol., July 15, 2004; 173(2): 1111 - 1117. [Abstract] [Full Text] [PDF]

				B. John and I. N. Crispe Passive and Active Mechanisms Trap Activated CD8+ T Cells in the Liver J. Immunol., May 1, 2004; 172(9): 5222 - 5229. [Abstract] [Full Text] [PDF]

				M. J. Fuller, A. Khanolkar, A. E. Tebo, and A. J. Zajac Maintenance, Loss, and Resurgence of T Cell Responses During Acute, Protracted, and Chronic Viral Infections J. Immunol., April 1, 2004; 172(7): 4204 - 4214. [Abstract] [Full Text] [PDF]

				L. A. Rudner, J. T. Lin, I.-K. Park, J. M. M. Cates, D. A. Dyer, D. M. Franz, M. A. French, E. M. Duncan, H. D. White, and J. D. Gorham Necroinflammatory Liver Disease in BALB/c Background, TGF-{beta}1-Deficient Mice Requires CD4+ T Cells J. Immunol., May 1, 2003; 170(9): 4785 - 4792. [Abstract] [Full Text] [PDF]

				B. A. Rabinovich, J. Li, J. Shannon, R. Hurren, J. Chalupny, D. Cosman, and R. G. Miller Activated, But Not Resting, T Cells Can Be Recognized and Killed by Syngeneic NK Cells J. Immunol., April 1, 2003; 170(7): 3572 - 3576. [Abstract] [Full Text] [PDF]

				J.-Y. Yoo and S. Desiderio Innate and acquired immunity intersect in a global view of the acute-phase response PNAS, February 4, 2003; 100(3): 1157 - 1162. [Abstract] [Full Text] [PDF]