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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lawrence, C. W. Articles by Braciale, T. J. Search for Related Content PubMed PubMed Citation Articles by Lawrence, C. W. Articles by Braciale, T. J.

Activation, Differentiation, and Migration of Naive Virus-Specific CD8⁺ T Cells during Pulmonary Influenza Virus Infection¹

Christopher W. Lawrence^*, and Thomas J. Braciale^2,*,,

^* Beirne B. Carter Center for Immunology Research, and Departments of Microbiology and Pathology, University of Virginia Health Sciences Center, Charlottesville, VA 22908

The low precursor frequency of individual virus-specific CD8⁺ T cells in a naive host makes the early events of CD8⁺ T cell activation, proliferation, and differentiation in response to viral infection a challenge to identify. We have therefore examined the response of naive CD8⁺ T cells to pulmonary influenza virus infection with a murine adoptive transfer model using hemagglutinin-specific TCR transgenic CD8⁺ T cells. Initial activation of CD8⁺ T cells occurs during the first 3 days postinfection exclusively within the draining lymph nodes. Acquisition of CTL effector functions, including effector cytokine and granule-associated protease expression, occurs in the draining lymph nodes and differentially correlates with cell division. Division of activated CD8⁺ T cells within the draining lymph nodes occurs in an asynchronous manner between days 3 and 4 postinfection. Despite the presence of Ag for several days within the draining lymph nodes, dividing T cells do not appear to maintain contact with residual Ag. After multiple cell divisions, CD8⁺ T cells exit the draining lymph nodes and migrate to the infected lung. Activated CD8⁺ T cells also disseminate throughout lymphoid tissue including the spleen and distal lymph nodes following their emigration from draining lymph nodes. These results demonstrate an important role for draining lymph nodes in orchestrating T cell responses during a local infection of a discrete organ to generate effector CD8⁺ T cells capable of responding to infection and seeding peripheral lymphoid tissues.

This article has been cited by other articles:

				C. C. Brinkman, S. L. Sheasley-O'Neill, A. R. Ferguson, and V. H. Engelhard Activated CD8 T Cells Redistribute to Antigen-Free Lymph Nodes and Exhibit Effector and Memory Characteristics J. Immunol., August 1, 2008; 181(3): 1814 - 1824. [Abstract] [Full Text] [PDF]

				J. McGill, N. Van Rooijen, and K. L. Legge Protective influenza-specific CD8 T cell responses require interactions with dendritic cells in the lungs J. Exp. Med., July 7, 2008; 205(7): 1635 - 1646. [Abstract] [Full Text] [PDF]

				D. K. Meyerholz, M. Edsen-Moore, J. McGill, R. A. Coleman, R. T. Cook, and K. L. Legge Chronic Alcohol Consumption Increases the Severity of Murine Influenza Virus Infections J. Immunol., July 1, 2008; 181(1): 641 - 648. [Abstract] [Full Text] [PDF]

				R. Kushwah, H. Cao, and J. Hu Characterization of Pulmonary T Cell Response to Helper-Dependent Adenoviral Vectors following Intranasal Delivery J. Immunol., March 15, 2008; 180(6): 4098 - 4108. [Abstract] [Full Text] [PDF]

				M. A. Fernandez, F. K. Puttur, Y. M. Wang, W. Howden, S. I. Alexander, and C. A. Jones T Regulatory Cells Contribute to the Attenuated Primary CD8+ and CD4+ T Cell Responses to Herpes Simplex Virus Type 2 in Neonatal Mice J. Immunol., February 1, 2008; 180(3): 1556 - 1564. [Abstract] [Full Text] [PDF]

				C.-H. Shen, Q. Ge, O. Talay, H. N. Eisen, A. Garcia-Sastre, and J. Chen Loss of IL-7R and IL-15R Expression Is Associated with Disappearance of Memory T Cells in Respiratory Tract following Influenza Infection J. Immunol., January 1, 2008; 180(1): 171 - 178. [Abstract] [Full Text] [PDF]

				M. R. Jenkins, K. Kedzierska, P. C. Doherty, and S. J. Turner Heterogeneity of Effector Phenotype for Acute Phase and Memory Influenza A Virus-Specific CTL J. Immunol., July 1, 2007; 179(1): 64 - 70. [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]

				H. Yoon, K. L. Legge, S.-s. J. Sung, and T. J. Braciale Sequential Activation of CD8+ T Cells in the Draining Lymph Nodes in Response to Pulmonary Virus Infection J. Immunol., July 1, 2007; 179(1): 391 - 399. [Abstract] [Full Text] [PDF]

				M. M. Anis, S. A. Fulton, S. M. Reba, C. V. Harding, and W. H. Boom Modulation of Naive CD4+ T-Cell Responses to an Airway Antigen during Pulmonary Mycobacterial Infection Infect. Immun., May 1, 2007; 75(5): 2260 - 2268. [Abstract] [Full Text] [PDF]

				S. L. Sheasley-O'Neill, C. C. Brinkman, A. R. Ferguson, M. C. Dispenza, and V. H. Engelhard Dendritic Cell Immunization Route Determines Integrin Expression and Lymphoid and Nonlymphoid Tissue Distribution of CD8 T Cells J. Immunol., February 1, 2007; 178(3): 1512 - 1522. [Abstract] [Full Text] [PDF]

				M. J. Dobrzanski, J. B. Reome, J. C. Hylind, and K. A. Rewers-Felkins CD8-Mediated Type 1 Antitumor Responses Selectively Modulate Endogenous Differentiated and Nondifferentiated T Cell Localization, Activation, and Function in Progressive Breast Cancer J. Immunol., December 1, 2006; 177(11): 8191 - 8201. [Abstract] [Full Text] [PDF]

				M. E. Wikstrom, E. Batanero, M. Smith, J. A. Thomas, C. von Garnier, P. G. Holt, and P. A. Stumbles Influence of Mucosal Adjuvants on Antigen Passage and CD4+ T Cell Activation during the Primary Response to Airborne Allergen J. Immunol., July 15, 2006; 177(2): 913 - 924. [Abstract] [Full Text] [PDF]

				J. K. Whitmire, N. Benning, and J. L. Whitton Precursor Frequency, Nonlinear Proliferation, and Functional Maturation of Virus-Specific CD4+ T Cells. J. Immunol., March 1, 2006; 176(5): 3028 - 3036. [Abstract] [Full Text] [PDF]

				M. Millrain, D. Scott, C. Addey, H. Dewchand, P. Ellis, I. Ehrmann, M. Mitchell, P. Burgoyne, E. Simpson, and J. Dyson Identification of the Immunodominant HY H2-Dk Epitope and Evaluation of the Role of Direct and Indirect Antigen Presentation in HY Responses J. Immunol., December 1, 2005; 175(11): 7209 - 7217. [Abstract] [Full Text] [PDF]

				C. C. Clay, D. S. Rodrigues, D. J. Harvey, C. M. Leutenegger, and U. Esser Distinct Chemokine Triggers and In Vivo Migratory Paths of Fluorescein Dye-Labeled T Lymphocytes in Acutely Simian Immunodeficiency Virus SIVmac251-Infected and Uninfected Macaques J. Virol., November 1, 2005; 79(21): 13759 - 13768. [Abstract] [Full Text] [PDF]

				D. R. Drake III, R. M. Ream, C. W. Lawrence, and T. J. Braciale Transient Loss of MHC Class I Tetramer Binding after CD8+ T Cell Activation Reflects Altered T Cell Effector Function J. Immunol., August 1, 2005; 175(3): 1507 - 1515. [Abstract] [Full Text] [PDF]

				C. W. Lawrence, R. M. Ream, and T. J. Braciale Frequency, Specificity, and Sites of Expansion of CD8+ T Cells during Primary Pulmonary Influenza Virus Infection J. Immunol., May 1, 2005; 174(9): 5332 - 5340. [Abstract] [Full Text] [PDF]

				S. Mrusek, S. Vallbracht, and S. Ehl The impact of splenectomy on antiviral T cell memory in mice Int. Immunol., January 1, 2005; 17(1): 27 - 33. [Abstract] [Full Text] [PDF]