Derivation and fluidity of acutely induced dysfunctional CD8+ T cells.

Publication/Presentation Date

4-15-2008

Abstract

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.

Volume

180

Issue

8

First Page

5300

Last Page

5308

ISSN

0022-1767

Disciplines

Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods

PubMedID

18390711

Department(s)

Administration and Leadership

Document Type

Article

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