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Department of Microbiology, University of Alabama, Birmingham, AL 35294
To evaluate the impact of sustained viral loads on anti-viral T
cell responses we compared responses that cleared acute lymphocytic
choriomeningitis virus infection with those that were elicited but
could not resolve chronic infection. During acute infection, as
replicating virus was cleared, CD8 T cell responses were
down-regulated, and a pool of resting memory cells developed. In
chronically infected hosts, the failure to control the infection was
associated with pronounced and prolonged activation of virus-specific
CD8 T cells. Nevertheless, there was a progressive diminution of their
effector activities as their capacity to produce first IL-2, then
TNF-
, and finally IFN-
was lost. Chronic lymphocytic
choriomeningitis virus infection was also associated with differential
contraction of certain CD8 T cell responses, resulting in altered
immunodominance. However, this altered immunodominance was not due to
selective expansion of T cells expressing particular TCR V
segments
during chronic infection. High viral loads were not only associated
with the ablation of CD8 T cell responses, but also with impaired
production of IL-2 by virus-specific CD4 T cells. Taken together, our
data show that sustained exposure to high viral loads results in the
progressive functional inactivation of virus-specific T cell responses,
which may further promote virus persistence.
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N. G. Laniewski and J. M. Grayson Antioxidant Treatment Reduces Expansion and Contraction of Antigen-Specific CD8+ T Cells during Primary but Not Secondary Viral Infection J. Virol., October 15, 2004; 78(20): 11246 - 11257. [Abstract] [Full Text] [PDF]
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X. Z. Wang, M. A. Brehm, and R. M. Welsh Preapoptotic Phenotype of Viral Epitope-Specific CD8 T Cells Precludes Memory Development and Is an Intrinsic Property of the Epitope J. Immunol., October 15, 2004; 173(8): 5138 - 5147. [Abstract] [Full Text] [PDF]
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A. Sanchez, M. Lukwiya, D. Bausch, S. Mahanty, A. J. Sanchez, K. D. Wagoner, and P. E. Rollin Analysis of Human Peripheral Blood Samples from Fatal and Nonfatal Cases of Ebola (Sudan) Hemorrhagic Fever: Cellular Responses, Virus Load, and Nitric Oxide Levels J. Virol., October 1, 2004; 78(19): 10370 - 10377. [Abstract] [Full Text] [PDF]
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M. Basler, N. Youhnovski, M. van den Broek, M. Przybylski, and M. Groettrup Immunoproteasomes Down-Regulate Presentation of a Subdominant T Cell Epitope from Lymphocytic Choriomeningitis Virus J. Immunol., September 15, 2004; 173(6): 3925 - 3934. [Abstract] [Full Text] [PDF]
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J. A. Rutigliano and B. S. Graham Prolonged Production of TNF-{alpha} Exacerbates Illness during Respiratory Syncytial Virus Infection J. Immunol., September 1, 2004; 173(5): 3408 - 3417. [Abstract] [Full Text] [PDF]
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E. J. Wherry and R. Ahmed Memory CD8 T-Cell Differentiation during Viral Infection J. Virol., June 1, 2004; 78(11): 5535 - 5545. [Full Text] [PDF]
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E. R. Piriou, K. van Dort, N. M. Nanlohy, F. Miedema, M. H. van Oers, and D. van Baarle Altered EBV Viral Load Setpoint after HIV Seroconversion Is in Accordance with Lack of Predictive Value of EBV Load for the Occurrence of AIDS-Related Non-Hodgkin Lymphoma J. Immunol., June 1, 2004; 172(11): 6931 - 6937. [Abstract] [Full Text] [PDF]
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S. Zhou, R. Ou, L. Huang, G. E. Price, and D. Moskophidis Differential Tissue-Specific Regulation of Antiviral CD8+ T-Cell Immune Responses during Chronic Viral Infection J. Virol., April 1, 2004; 78(7): 3578 - 3600. [Abstract] [Full Text] [PDF]
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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]
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A. Khanolkar, M. J. Fuller, and A. J. Zajac CD4 T Cell-Dependent CD8 T Cell Maturation J. Immunol., March 1, 2004; 172(5): 2834 - 2844. [Abstract] [Full Text] [PDF]
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S.-K. Kim and R. M. Welsh Comprehensive Early and Lasting Loss of Memory CD8 T Cells and Functional Memory during Acute and Persistent Viral Infections J. Immunol., March 1, 2004; 172(5): 3139 - 3150. [Abstract] [Full Text] [PDF]
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B. E. Palmer, E. Boritz, and C. C. Wilson Effects of Sustained HIV-1 Plasma Viremia on HIV-1 Gag-Specific CD4+ T Cell Maturation and Function J. Immunol., March 1, 2004; 172(5): 3337 - 3347. [Abstract] [Full Text] [PDF]
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K. Tewari, J. Sacha, X. Gao, and M. Suresh Effect of Chronic Viral Infection on Epitope Selection, Cytokine Production, and Surface Phenotype of CD8 T Cells and the Role of IFN-{gamma} Receptor in Immune Regulation J. Immunol., February 1, 2004; 172(3): 1491 - 1500. [Abstract] [Full Text] [PDF]
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K. Abel, L. La Franco-Scheuch, T. Rourke, Z.-M. Ma, V. de Silva, B. Fallert, L. Beckett, T. A. Reinhart, and C. J. Miller Gamma Interferon-Mediated Inflammation Is Associated with Lack of Protection from Intravaginal Simian Immunodeficiency Virus SIVmac239 Challenge in Simian-Human Immunodeficiency Virus 89.6-Immunized Rhesus Macaques J. Virol., January 15, 2004; 78(2): 841 - 854. [Abstract] [Full Text] [PDF]
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S.-A. Younes, B. Yassine-Diab, A. R. Dumont, M.-R. Boulassel, Z. Grossman, J.-P. Routy, and R.-P. Sekaly HIV-1 Viremia Prevents the Establishment of Interleukin 2-producing HIV-specific Memory CD4+ T Cells Endowed with Proliferative Capacity J. Exp. Med., December 15, 2003; 198(12): 1909 - 1922. [Abstract] [Full Text] [PDF]
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C. Iyasere, J. C. Tilton, A. J. Johnson, S. Younes, B. Yassine-Diab, R.-P. Sekaly, W. W. Kwok, S. A. Migueles, A. C. Laborico, W. L. Shupert, et al. Diminished Proliferation of Human Immunodeficiency Virus-Specific CD4+ T Cells Is Associated with Diminished Interleukin-2 (IL-2) Production and Is Recovered by Exogenous IL-2 J. Virol., October 15, 2003; 77(20): 10900 - 10909. [Abstract] [Full Text] [PDF]
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