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Functional Plasticity in Memory T Helper Cell Responses¹

Connie M. Krawczyk^*, Hao Shen and Edward J. Pearce^2,*

^* Department of Pathobiology, School of Veterinary Medicine, and Department of Microbiology, School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104

Following activation, naive CD4⁺ Th cells can differentiate to selectively produce either the Th1 lineage-specific cytokine IFN- or the Th2 cytokine IL-4 and, in so doing, lose the capacity to produce cytokines of the alternative lineage. Lineage commitment of murine CD4⁺ T cells has largely been considered to be absolute with little flexibility to produce cytokines of the opposing lineage. In this study, we demonstrate that cells within Th2 memory populations can produce IFN- if reactivated in vivo in the context of an innate response that favors Th1 cell development. Likewise, cells within Th1 memory populations produce IL-4 when challenged under conditions that promote Th2 responses. Both effector and unpolarized central memory cells retain the potential to produce cytokines that were not made during the primary response. These findings reveal that both effector and central memory Th1 and Th2 cells possess the capacity to respond to environmental cues to produce pathogen-appropriate cytokines of the opposing lineage.

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 Grants AI53825 (to E.J.P.) and AI45025 (to H.S.). E.J.P. is a Burroughs Wellcome Fund Scholar in Molecular Parasitology. C.M.K. is supported by the Canadian Institutes of Health Research and the International Human Frontier Science Program Organization.

² Address correspondence and reprint requests to Dr. Edward J. Pearce, Department of Pathobiology, Room 3818 Hill Pavilion, School of Veterinary Medicine, 380 South University Avenue, Philadelphia, PA 19104. E-mail address: ejpearce{at}mail.med.upenn.edu

³ Abbreviations used in this paper: Thp, Th precursor; DC, dendritic cell; EDC, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride; ICS, intracellular cytokine staining; LCMV, lymphocytic choriomeningitis virus; LLO, listeriolysin O; Lm, Listeria monocytogenes; LLO₁₉₀, peptide containing aa 190–201 of the Lm LLO protein; seallo, LLO₁₉₀-SEA conjugate; PA, Propionibacterium acnes; SEA, soluble Schistosoma mansoni egg antigen; Tcm, central memory Th cell; Tem, effector memory Th cell.

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