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Human CD4⁺ Memory T Cells Are Preferential Targets for Bystander Activation and Apoptosis¹

Sarah C. Bangs^*, Dilair Baban^2,, Helen J. Cattan, Chris Ka-Fi Li^*, Andrew J. McMichael^* and Xiao-Ning Xu^3,*

^* Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom; Medical Research Council Functional Genetics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom; and Medical Research Council Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, United Kingdom

There is much evidence that T cells may be activated via mechanisms that act independently of direct TCR ligation. Despite this, the question of whether such forms of bystander T cell activation occur during immune responses is hotly debated. To address some outstanding questions, we set up an in vitro system within which to analyze bystander T cell activation in human T cells, in the absence of the possibility for TCR cross-reactivity. In addition, we have investigated the genetic, phenotypic, and functional characteristics of bystander-activated T cells. In this study, we show that bystander T cell activation is, indeed, observed during a specific immune response, and that it occurs preferentially among CD4⁺ memory T cells. Furthermore, bystander-activated T cells display a distinct gene expression profile. The mechanism for bystander T cell activation involves soluble factors, and the outcome is an elevated level of apoptosis. This may provide an explanation for the attrition of T cell memory pools of heterologous specificity during immune responses to pathogens such as viruses.

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 funding from the United Kingdom Medical Research Council.

² Current address: Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford, OX3 7BN, U.K.

³ Address correspondence and reprint requests to Dr. Xiao-Ning Xu, Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Headington, Oxford, OX3 9DS, U.K. E-mail address: xiaoning.xu{at}imm.ox.ac.uk

⁴ Abbreviations used in this paper: SEB, staphylococcal enterotoxin B; LCMV, lymphocytic choriomeningitis virus; MFI, mean fluorescence intensity.

⁵ The online version of this article contains supplemental material.

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The JI 2009 182: 1777-1778. [Full Text]