Direct recognition of LPS by human but not murine CD8+ T cells via TLR4 complex

Komai-Koma, M., Gilchrist, D. S. and Xu, D. (2009) Direct recognition of LPS by human but not murine CD8+ T cells via TLR4 complex. European Journal of Immunology, 39(6), pp. 1564-1572. (doi: 10.1002/eji.200838866)

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LPS comprises a major PAMP and is a key target of the immune system during bacterial infection. While LPS can be recognised by innate immune cells via the TLR4 complex, it is unknown whether T lymphocytes, especially CD8<sup>+</sup> T cells are also capable of doing so. We report here that naïve human CD8<sup>+</sup> T cells, after activation by TCR stimulation, express surface TLR4 and CD14. These activated CD8<sup>+</sup> T cells can then secrete high concentrations of IFN-γ, granzyme and perforin in response to LPS. These effects can be specifically inhibited using siRNA for TLR4. Furthermore, LPS can synergise with IL-12 to polarise the CD8<sup>+</sup> T cells into cytotoxic T-cell 1 (Tc1) that produce IFN-γ but not IL-4, with or without TCR activation. Moreover, CD8<sup>+</sup> CD45RO<sup>+</sup> memory T cells constitutively expressed TLR4 and markedly enhanced IFN-γ production when stimulated with LPS. In contrast, activated murine CD8<sup>+</sup> T cells lack TLR4 and CD14 expression and fail to respond to LPS for proliferation and cytokine production. Thus, human but not murine CD8<sup>+</sup> T cells are able to directly recognise bacterial LPS via LPS receptor complex and TLR4 provides a novel signal for the activation of effector and memory human CD8<sup>+</sup> T cells.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Xu, Dr Damo and Komai-Koma, Dr Mousa and Gilchrist, Dr Derek
Authors: Komai-Koma, M., Gilchrist, D. S., and Xu, D.
College/School:College of Medical Veterinary and Life Sciences
Journal Name:European Journal of Immunology
Journal Abbr.:Eur. J. Immunol.
Publisher:Wiley-VCH Verlag
ISSN (Online):1521-4141
Published Online:29 April 2009
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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
241511Characterisation of genes differentially expressed on subsets of T lymphocytesFoo LiewMedical Research Council (MRC)G9818261Infection Immunity and Inflammation Medicine
486461The role of IL-35 in infection and inflammationFoo LiewMedical Research Council (MRC)G0801198III -IMMUNOLOGY