Journal
EUROPEAN JOURNAL OF IMMUNOLOGY
Volume 39, Issue 6, Pages 1564-1572Publisher
WILEY
DOI: 10.1002/eji.200838866
Keywords
CD14; CD8(+) T cells; Tc1; LPS; TLR
Categories
Funding
- European Union, Medical Research Council, UK
- Wellcome Trust
- MRC [G9818261, G0801198] Funding Source: UKRI
- Medical Research Council [G0801198, G9818261] Funding Source: researchfish
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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(+) T cells are also capable of doing so. We report here that naive human CD8(+) T cells, after activation by TCR stimulation, express surface TLR4 and CD14. These activated CD8(+) T cells can then secrete high concentrations of IFN-gamma, 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(+) T cells into cytotoxic T-cell 1 (Tc1) that produce IFN-gamma but not IL-4, with or without TCR activation. Moreover, CD8(+)CD45RO(+) memory T cells constitutively expressed TLR4 and markedly enhanced IFN-gamma production when stimulated with LPS. In contrast, activated murine CD8(+) T cells lack TLR4 and CD14 expression and fail to respond to LPS for proliferation and cytokine production. Thus, human but not murine CD8(+) 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(+) T cells.
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