TLR2 is expressed on activated T cells as a costimulatory receptor

Abstract

Toll is the founder of a group of pattern recognition receptors that play a critical role in the innate immunity in Drosophila. At least 10 distinct Toll-like receptors (TLRs), recognizing pathogen-associated molecular patterns, have now been identified in humans. Most investigations on TLRs have focused on cells of the innate system. We report here that naïve human T cells expressed high levels of cellsurface TLR2 after activation by anti-T cell receptor antibody and IFN-␣. Activated cells produced elevated levels of cytokines in response to the TLR2 ligand, bacterial lipopeptide. Furthermore, CD4 ؉ CD45RO ؉ memory T cells from peripheral blood constitutively expressed TLR2 and produced IFN-␥ in response to bacterial lipopeptide, which also markedly enhanced the proliferation and IFN-␥ production by CD45RO ؉ T cells in the presence of IL-2 or IL-15. Thus, TLR2 serves as a costimulatory receptor for antigen-specific T cell development and participates in the maintenance of T cell memory. This suggests that pathogens, via their pathogen-associated molecular patterns, may contribute directly to the perpetuation and activation of long-term T cell memory in both antigen-dependent and independent manner.

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

“…While the mechanism is still unclear and currently under investigation, this is in agreement with the previous findings that BLP preferentially promotes human and murine Th1 but not Th2 cell differentiation [7,8] and that TLR agonists selectively stimulate IFN-g but not IL-4 production by human gd T cells [9,10,12]. Our results therefore support current evidence and suggest the existence of a novel type I T-cell development pathway by directly recognising PAMP via TLRs on T cells.While human and murine T cells have the same ability in BLP recognition, the visualisation of LPS appears to be human CD8 1 T-cell specific, since human CD4 1 and murine CD8 1 T cells fail to do so [7]. This is in line with several reports that LPS stimulates murine CD8 1 T activation in vivo via an indirect pathway involving APC [17,18,26].…”

“…This was subsequently confirmed in mice [8]. Furthermore, human and murine memory T cells constitutively express surface TLRs and directly recognise TLR agonists [7,9,10]. Moreover, TLR agonists directly promote further TLR expression, survival and the function of NKT and gd T cells [11,12].…”

“…Growing evidence suggests that T cells participate in immune microbial surveillance [7][8][9][10]. We reported for the first time that human CD4 1 T cells express functional TLR2 and that TLR2 signals directly promote T-cell function [7].…”

“…39: 1564-1572 Immunomodulation The reason why there is a difference in proliferation but not cytokine production between naïve and memory T cells in the responsiveness to anti-CD3 and LPS stimulation is not fully understood. However, T-cell proliferation is not always correlated with cytokine expression [7]. This may be because cytokine production and cell proliferation demands on different signals and the proliferating cells may not be necessary for the cytokine producing cells.…”

NF-κB and the immune response

“…For example, it has been observed that homeostatic polyclonal activation of B cells, which results in the so-called serological memory, that is, detectable antibody to antigens that are no longer present in the host, can be induced/ maintained by TLR ligation (Bernasconi et al, 2002). Analogously, TLR2 is upregulated in CD4 þ T cells following TCR stimulation, and TLR2 ligands may thus provide an activation/maintenance signal in these cells (Komai-Koma et al, 2004). That signaling through TLRs in these aspects of B-cell responses requires NF-kB seems likely, but has yet to be demonstrated.…”