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Derivation and Fluidity of Acutely Induced Dysfunctional CD8⁺ T Cells¹

Gabriela Plesa^*, Adam E. Snook, Scott A. Waldman and Laurence C. Eisenlohr^2,*

^* Department of Microbiology and Immunology and Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, PA 19107

Dysfunctional CD8⁺ T (T_CD8⁺) cells lacking cytokine production have been identified in many viral infections, but their genesis is not well understood. Established results indicate that such cells could be either high avidity that enter a refractory state due to overstimulation or low avidity that are only partially stimulated. Using an acute, resolving infection model that results in rapid production of dysfunctional cells, we show that this IL2 unresponsive phenotype emerges from the low end of the avidity spectrum and is characterized by broad TCR usage and a reduced proliferation rate. Furthermore, the dysfunctional population is extremely fluid, being sustained by high Ag dose but virtually eliminated following low dose boosting. Together, these results suggest that persistence of dysfunctional cells generated in this manner depends upon continual exposure to high Ag levels and that such cells may ultimately predominate if functional cells become exhausted.

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 by National Institutes of Health Grant AI046511.

² Address correspondence and reprint requests to Dr. Laurence C. Eisenlohr, Thomas Jefferson University, 233 South 10th Street, Bluemie Life Sciences Building 730, Philadelphia, PA 19107. E-mail address: Laurence.Eisenlohr{at}jefferson.edu

³ Abbreviations used in this paper: Vac, vaccinia virus; RV, rabies virus; Flu, influenza; Adeno, adenovirus; MFI, mean fluorescence intensity; ICS, intracellular staining.

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The JI 2008 180: 5155-5156. [Full Text]  

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