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De Novo Recruitment of Antigen-Experienced and Naive T Cells Contributes to the Long-Term Maintenance of Antiviral T Cell Populations in the Persistently Infected Central Nervous System¹

Jingxian Zhao,^* Jincun Zhao,^* and Stanley Perlman^2*

^*Department of Microbiology, University of Iowa, Iowa City, IA 52242; and Institute for Tissue Transplantation and Immunology, Jinan University, Guangzhou, China

Mice infected with attenuated strains of mouse hepatitis virus, strain JHM, develop a chronic infection in the brain and spinal cord characterized by low levels of viral Ag persistence and retention of virus-specific CD4 and CD8 T cells at the site of infection. It is not known whether these cells are maintained by proliferation of T cells that entered the CNS during acute infection or are newly recruited from Ag-experienced or naive T cell pools. In this study, using adoptive transfer experiments and bone marrow chimeras, we show that at least some of these cells are recruited from the periphery, predominantly from the viral Ag-experienced T cell pool. Both virus-specific CD4 and CD8 T cells are functional, as assessed by cytokine expression and degranulation after peptide exposure. In addition, populations of virus-specific CD4 T cells undergo dynamic changes in the infected CNS, as previously shown for CD8 T cells, because ratios of cells responding to two CD4 T cell epitopes change by a factor of five during the course of persistence. Collectively, these results show that maintenance of T cell responses in the virus-infected CNS is a dynamic process. Further, virus-specific T cell numbers at this site of infection are maintained by recruitment from peripheral Ag-experienced and naive T cell pools.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported in part by Grants from the National Institutes of Health (NS36592) and National Multiple Sclerosis Society (RG 2864).

² Address correspondence and reprint requests to Dr. Stanley Perlman, Department of Microbiology, University of Iowa, Bowen Science Building 3-712, Iowa City, IA 52242. E-mail address: Stanley-Perlman{at}uiowa.edu

³ Abbreviations used in this paper: p.i., post infection; LCMV, lymphocytic choriomeningitis virus; CLN, cervical lymph node.

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The JI 2009 183: 4829-4830. [Full Text]