The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1998/12/2205/ $5.00
The Journal of Experimental Medicine, Volume 188, Number 12, December 21, 1998 2205-2213

Articles

Viral Immune Evasion Due to Persistence of Activated T Cells Without Effector Function

Allan J. Zajac, Joseph N. Blattman, Kaja Murali-Krishna, David J.D. Sourdive, M. Suresh, John D. Altman, and Rafi Ahmed

From the Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia 30322

We examined the regulation of virus-specific CD8 T cell responses during chronic lymphocytic choriomeningitis virus (LCMV) infection of mice. Our study shows that within the same persistently infected host, different mechanisms can operate to silence antiviral T cell responses; CD8 T cells specific to one dominant viral epitope were deleted, whereas CD8 T cells responding to another dominant epitope persisted indefinitely. These virus-specific CD8 T cells expressed activation markers (CD69hi, CD44hi, CD62Llo) and proliferated in vivo but were unable to elaborate any antiviral effector functions. This unresponsive phenotype was more pronounced under conditions of CD4 T cell deficiency, highlighting the importance of CD8– CD4 T cell collaboration in controlling persistent infections. Importantly, in the presence of CD4 T cell help, adequate CD8 effector activity was maintained and the chronic viral infection eventually resolved. The persistence of activated virus-specific CD8 T cells without effector function reveals a novel mechanism for silencing antiviral immune responses and also offers new possibilities for enhancing CD8 T cell immunity in chronically infected hosts.

Key Words: cytotoxic T cells • unresponsiveness • chronic infections • CD4 T cells • major histocompatibility complex tetramers

Address correspondence to Rafi Ahmed, Emory Vaccine Center, Emory University School of Medicine, G211 Rollins Research Bldg., 1510 Clifton Rd., Atlanta, GA 30322. Phone: 404-727-4700; Fax: 404-727-3722; E-mail: ra{at}microbio.emory.edu

Abbreviations used: +/+ mice, C57BL/6J mice; BrdU, 5-bromo-2'-deoxyuridine; CD4–/–, CD4-deficient; GP, glycoprotein; LCMV, lymphocytic choriomeningitis virus; NP, nucleoprotein.


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