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

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.