Am. J. Respir. Cell Mol. Biol., Volume 25, Number 3, September, 2001 362-369

Type II Pneumocyte-CD8+ T-Cell Interactions
Relationship between Target Cell Cytotoxicity and Activation

Min Q. Zhao, Mana K. Amir, Ward R. Rice, and Richard I. Enelow

Department of Medicine and the Beirne B. Carter Center for Immunology Research, University of Virginia School of Medicine, Charlottesville, Virginia; and Children's Hospital Medical Center, Cincinnati, Ohio

CD8+ T-cell responses play an important role in the clearance of respiratory virus infection, but may also contribute to lung injury in the process. The effector mechanisms involved in viral clearance and associated lung injury include both cytolytic and noncytolytic effector functions. Previously we have shown that CD8+ T-cell recognition of alveolar epithelial cells triggers chemokine expression by the epithelial cell and that this plays an important role in the inflammatory infiltration that ensues in the context of T cell-mediated injury (Zhao and colleagues, J. Clin. Invest. 2000;106:R49-R58). In the present study we sought to understand the relationship between alveolar cell cytotoxicity and chemokine expression, both of which occur as a result of CD8+ T-cell antigen recognition. Alveolar epithelial cells efficiently process and present overlapping viral epitopes, and CD8+ T-cell recognition of these class I major histocompatibility complex-restricted epitopes resulted in cytotoxicity of the alveolar cells by both wild-type and perforin-deficient T cells. However, the contribution of perforin-mediated lysis to the total cytotoxicity of alveolar cells by CD8+ T cells was minimal, and the majority of the lysis was attributable to tumor necrosis factor- expressed by the T cell. CD8+ T-cell recognition also led to activation of nuclear factor-B in the alveolar epithelial target cells, at levels inversely proportional to the effector/target (E:T) ratio. Finally, at varying E:T ratios, we demonstrated an inverse relationship between alveolar cell cytotoxicity and monocyte chemotactic protein-1 expression, both of which occur as a result of T-cell recognition. These findings may have important ramifications in understanding the relationship between viral clearance and lung injury.

This article has been cited by other articles:

				E. G. Tzortzaki and N. M. Siafakas A hypothesis for the initiation of COPD Eur. Respir. J., August 1, 2009; 34(2): 310 - 315. [Abstract] [Full Text] [PDF]

				G. S. Pryhuber, H. L. Huyck, S. Bhagwat, M. A. O'Reilly, J. N. Finkelstein, F. Gigliotti, and T. W. Wright Parenchymal Cell TNF Receptors Contribute to Inflammatory Cell Recruitment and Respiratory Failure in Pneumocystis carinii-Induced Pneumonia J. Immunol., July 15, 2008; 181(2): 1409 - 1419. [Abstract] [Full Text] [PDF]

				S. Nikos "In the Beginning" of COPD: Is Evolution Important? Am. J. Respir. Crit. Care Med., March 1, 2007; 175(5): 423 - 424. [Full Text] [PDF]

				J. Liu, M. Q. Zhao, L. Xu, C. V. Ramana, W. Declercq, P. Vandenabeele, and R. I. Enelow Requirement for Tumor Necrosis Factor-Receptor 2 in Alveolar Chemokine Expression Depends upon the Form of the Ligand Am. J. Respir. Cell Mol. Biol., November 1, 2005; 33(5): 463 - 469. [Abstract] [Full Text] [PDF]

				G. C. Hildebrandt, K. M. Olkiewicz, L. A. Corrion, Y. Chang, S. G. Clouthier, C. Liu, and K. R. Cooke Donor-derived TNF-{alpha} regulates pulmonary chemokine expression and the development of idiopathic pneumonia syndrome after allogeneic bone marrow transplantation Blood, July 15, 2004; 104(2): 586 - 593. [Abstract] [Full Text] [PDF]

				G. C. Hildebrandt, U. A. Duffner, K. M. Olkiewicz, L. A. Corrion, N. E. Willmarth, D. L. Williams, S. G. Clouthier, C. M. Hogaboam, P. R. Reddy, B. B. Moore, et al. A critical role for CCR2/MCP-1 interactions in the development of idiopathic pneumonia syndrome after allogeneic bone marrow transplantation Blood, March 15, 2004; 103(6): 2417 - 2426. [Abstract] [Full Text] [PDF]

				N. Yokohori, K. Aoshiba, and A. Nagai Increased Levels of Cell Death and Proliferation in Alveolar Wall Cells in Patients With Pulmonary Emphysema Chest, February 1, 2004; 125(2): 626 - 632. [Abstract] [Full Text] [PDF]

				J. N. Vanderbilt, E. M. Mager, L. Allen, T. Sawa, J. Wiener-Kronish, R. Gonzalez, and L. G. Dobbs CXC Chemokines and Their Receptors Are Expressed in Type II Cells and Upregulated following Lung Injury Am. J. Respir. Cell Mol. Biol., December 1, 2003; 29(6): 661 - 668. [Abstract] [Full Text] [PDF]

				M. A. Olman and M. A. Matthay Transforming growth factor-{beta} induces fibrosis in immune cell-depleted lungs Am J Physiol Lung Cell Mol Physiol, September 1, 2003; 285(3): L522 - L526. [Full Text] [PDF]

				K. Aoshiba, N. Yokohori, and A. Nagai Alveolar Wall Apoptosis Causes Lung Destruction and Emphysematous Changes Am. J. Respir. Cell Mol. Biol., May 1, 2003; 28(5): 555 - 562. [Abstract] [Full Text] [PDF]