Differential regulation of effector- and central-memory responses to Toxoplasma gondii infection by IL-12 revealed by tracking of Tgd057-specific CD8+ T cells

Production of the pro-inflammatory cytokine il-12 by innate phagocytes drives the differentiation of ifn-c-producing effector t cells during toxoplasma gondii infection. however,the role of il-12 in the regulation of memory cd8+ t cell differentiation and function during murine toxoplasmosis is unclear. to track memory ctl development,we identified a novel h-2kb-restricted ctl population specific for the toxoplasma antigen tgd057. tgd057-specific ctls were induced by both vaccination and natural peroral infection,and were representative of the polyclonal ctl population. tgd057-specific primary effector cells required il-12 for the differentiation of klrg1+ effector subpopulations and ifn-γ production in response to restimulation with parasite-infected cells,but not to restimulation with cognate peptide. the effect of il-12 deficiency during the primary response was profoundly imprinted on memory ctls,which continued to show defects in cell numbers,klrg1+ effector memory subpopulation differentiation,and ifn-γ recall responses. importantly,isolated cd62lhi klrg1- cd8+ t cells differentiated in the absence of il-12 were enhanced in their ability to generate ifn-γ-producing secondary tgd057-specific effector cells. our data,for the first time,demonstrate the negative impact of il-12 signaling on the quality of the central memory ctl compartment. thus,despite the beneficial role of il-12 in promoting effector differentiation,excessive exposure to il-12 during ctl priming may limit the development of long-term protective immunity through the decreased fitness of central memory ctl responses. © 2010 wilson et al.