In innate memory CD8+ T cells, LPS upregulates IFN-γ and suppresses IL-10In antigen-experienced CD8+ T cells, ligands can induce rapid IFN-γ secretion in a TCR-independent manner, requiring T cell-intrinsic MyD88 signaling and IL-18R expressionIn RA-derived CD8+ T cells, aberrant TLR4 expression leads to direct activation by LPS, upregulating cytotoxic molecules (granzyme B, perforin) and inflammatory cytokines (TNF-α, IFN-γ) independent of TCR engagement. The gene discussed is GZMB; the disease is rheumatoid arthritis.