RESUMO
Memory CD8(+) T cells induced upon immunization exhibit improved functional features that contribute to protection of immunized hosts. Although both cognate antigen recognition and inflammation are important for memory CD8(+) T cell reactivation, the relative contribution of these factors and the cell types providing these signals in vivo are poorly defined. Here, we show that Ly6C(+)CCR2(+) inflammatory monocytes, a subset of monocytes, largely orchestrate memory CD8(+) T and NK lymphocytes activation by differentiating into interleukin-18 (IL-18)- and IL-15-producing cells in an inflammasome and type I interferon-IRF3-dependent manner. Memory CD8(+) T cells became potent effector cells by sensing inflammation from monocytes independently of their cognate antigen. Like NK cells, they underwent rapid mobilization, upregulated intense and sustained effector functions during bacterial, viral, and parasitic infections, and contributed to innate responses and protection in vivo. Thus, inflammatory monocyte-derived IL-18 and IL-15 are critical to initiate memory CD8(+) T and NK lymphocytes differentiation into antimicrobial effector cells.
Assuntos
Antígenos/imunologia , Linfócitos T CD8-Positivos/imunologia , Memória Imunológica/imunologia , Células Matadoras Naturais/imunologia , Monócitos/imunologia , Animais , Antígenos Ly/imunologia , Antígenos Ly/metabolismo , Infecções Bacterianas/imunologia , Infecções Bacterianas/microbiologia , Linfócitos T CD8-Positivos/metabolismo , Feminino , Citometria de Fluxo , Inflamação/imunologia , Interleucina-15/genética , Interleucina-15/imunologia , Interleucina-15/metabolismo , Interleucina-18/imunologia , Interleucina-18/metabolismo , Células Matadoras Naturais/metabolismo , Listeria monocytogenes/imunologia , Malária/imunologia , Malária/parasitologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Monócitos/metabolismo , Plasmodium berghei/imunologia , Receptores CCR2/genética , Receptores CCR2/imunologia , Receptores CCR2/metabolismo , Streptococcus pneumoniae/imunologiaRESUMO
Following microbial pathogen invasion, one of the main challenges for the host is to rapidly control pathogen spreading to avoid vital tissue damage. Here we report that an effector CD8(+) T-cell population that expresses the marker NK1.1 undergoes delayed contraction and sustains early anti-microbial protection. NK1.1(+) CD8(+) T cells are derived from CD8(+) T cells during priming, and their differentiation is inhibited by transforming growth factor-ß signalling. After their own contraction phase, they form a distinct pool of KLRG1 CD127 double-positive memory T cells and rapidly produce both interferon-γ and granzyme B, providing significant pathogen protection in an antigen-independent manner within only a few hours. Thus, by prolonging the CD8(+) T-cell response at the effector stage and by expressing exacerbated innate-like features at the memory stage, NK1.1(+) cells represent a distinct subset of CD8(+) T cell that contributes to the early control of microbial pathogen re-infections.