Responses to LPS boost effector CD8 T-cell accumulation outside of signals 1 and 2

Abstract

Immunization with adjuvant plus antigen induces durable T-cell immunity and is a mainstay of vaccines. Here, the consequence of separating antigen stimulation of T cells from the adjuvant response was studied in a re-transfer model. Effector CD8 T cells in recipient mice were exposed to lipopolysaccharide (LPS), the Toll-like receptor 4 (TLR4) ligand, which significantly increased persistence. While accumulation in lymphoid and non-lymphoid organs was evident, this result depended upon the timing of LPS administration and the presence of the TLR4 adaptor TRIF in the recipient mice. Interestingly, there was very little impact of the LPS response on subset differentiation, which rather appeared to be programmed by antigen and costimulation. To discern factors that limit accumulation, interleukin 10 (IL-10) was targeted since it is a product of TLR4 triggering and mitigates inflammation. Blockade of IL-10 increased accumulation even though the effector CD8 T cells were well past the priming phase, but upon recall interferon-γ secretion was not affected as would be expected when IL-10 is present during priming. Thus, the adjuvant-altered microenvironment is effective not only in the presence of antigen but also during a window of effector CD8 T-cell stasis, suggesting that pathogen-associated molecular pattern molecules released during co-infection, or by vaccines, could alter the survival fate of specific effector T cells.Cellular & Molecular Immunology advance online publication, 20 July 2015; doi:10.1038/cmi.2015.69.

A Mineralocorticoid Receptor Deficiency in Myeloid Cells Reduces Liver Steatosis by Impairing Activation of CD8+ T Cells in a Nonalcoholic Steatohepatitis Mouse Model

“…Despite we did not measure IL-18 levels in coculture supernatants, RT-PCRs performed in livers high levels of IL-18 in MCD-fed mice ( Supplementary Figure 2 ). In addition, direct stimulation of TLR ligands (such as LPS) can elicit effector CD8+ T cells to produce IFN-γ and modulates its accumulation in several lymphoid organs ( 50 ). We mention this point, because is only in the coculture with LPS matured DCs that differences in CD8+ T cell activation is seen.…”

Cellular and molecular regulation of innate inflammatory responses

“…Distinct set of PRRs in different species, tissues, cells or cellular organelles display a partially overlapped and compensated recognition of PAMPs during inflammatory conditions. LPS from Gram-negative bacteria, is crucial for TLR4 activation, but also initiates innate immune signaling via detection by cytosol caspase-4/5/11 in mammals, 90,91 while in plants via sensing by transmembrane receptor kinase LORE. LORE confers recognition of LPS in plants and the subsequent induction of an immune response.…”

Chronic Critical Illness from Sepsis Is Associated with an Enhanced TCR Response

“…A similar "priming" of T cells was also reported for mice during postacute septic peritonitis (21). Along the same lines, LPS (as the most widely used experimental trigger of systemic inflammation) or IL-1 (a proinflammatory cytokine released in most settings of systemic inflammation) reportedly prime T cells to an ensuing Ag encounter (57)(58)(59)(60)(61). In light of these data, our findings provide evidence of a primed, rather than a suppressed, T cell state (as defined by the strength of the TCR response) in the aftermath of sepsis.…”