Conventional T-bet+Foxp3- Th1 cells are the major source of host-protective regulatory IL-10 during intracellular protozoan infection

@article{citeulike:1402632, abstract = {Although interferon {gamma} (IFN-{gamma}) secretion is essential for control of most intracellular pathogens, host survival often also depends on the expression of interleukin 10 (IL-10), a cytokine known to counteract IFN-{gamma} effector functions. We analyzed the source of regulatory IL-10 in mice infected with the protozoan parasite Toxoplasma gondii. Unexpectedly, IFN-{gamma}-secreting T-bet+Foxp3- T helper type 1 (Th1) cells were found to be the major producers of IL-10 in these animals. Further analysis revealed that the same IL-10+IFN-{gamma}{gamma} population displayed potent effector function against the parasite while, paradoxically, also inducing profound suppression of IL-12 production by antigen-presenting cells. Although at any given time point only a fraction of the cells appeared to simultaneously produce IL-10 and IFN-{gamma}, IL-10 production could be stimulated in IL-10-IFN-{gamma}+ cells by further activation in vitro. In addition, experiments with T. gondii-specific IL-10+IFN-{gamma}+ CD4 clones revealed that although IFN-{gamma} expression is imprinted and triggered with similar kinetics regardless of the state of Th1 cell activation, IL-10 secretion is induced more rapidly from recently activated than from resting cells. These findings indicate that IL-10 production by CD4+ T lymphocytes need not involve a distinct regulatory Th cell subset but can be generated in Th1 cells as part of the effector response to intracellular pathogens. 10.1084/jem.20062175}, author = {Jankovic, Dragana and Kullberg, Marika C. and Feng, Carl G. and Goldszmid, Romina S. and Collazo, Carmen M. and Wilson, Mark and Wynn, Thomas A. and Kamanaka, Masahito and Flavell, Richard A. and Sher, Alan }, citeulike-article-id = {1402632}, doi = {10.1084/jem.20062175}, journal = {J. Exp. Med.}, keywords = {il-10-tcells}, month = {February}, number = {2}, pages = {273--283}, posted-at = {2007-06-21 16:11:46}, priority = {2}, title = {Conventional T-bet+Foxp3- Th1 cells are the major source of host-protective regulatory IL-10 during intracellular protozoan infection}, url = {http://dx.doi.org/10.1084/jem.20062175}, volume = {204}, year = {2007} }

TY - JOUR ID - citeulike:1402632 L3 - citeulike-article-id:1402632 TI - Conventional T-bet+Foxp3- Th1 cells are the major source of host-protective regulatory IL-10 during intracellular protozoan infection JF - J. Exp. Med. VL - 204 IS - 2 SP - 273 EP - 283 N2 - Although interferon {gamma} (IFN-{gamma}) secretion is essential for control of most intracellular pathogens, host survival often also depends on the expression of interleukin 10 (IL-10), a cytokine known to counteract IFN-{gamma} effector functions. We analyzed the source of regulatory IL-10 in mice infected with the protozoan parasite Toxoplasma gondii. Unexpectedly, IFN-{gamma}-secreting T-bet+Foxp3- T helper type 1 (Th1) cells were found to be the major producers of IL-10 in these animals. Further analysis revealed that the same IL-10+IFN-{gamma}{gamma} population displayed potent effector function against the parasite while, paradoxically, also inducing profound suppression of IL-12 production by antigen-presenting cells. Although at any given time point only a fraction of the cells appeared to simultaneously produce IL-10 and IFN-{gamma}, IL-10 production could be stimulated in IL-10-IFN-{gamma}+ cells by further activation in vitro. In addition, experiments with T. gondii-specific IL-10+IFN-{gamma}+ CD4 clones revealed that although IFN-{gamma} expression is imprinted and triggered with similar kinetics regardless of the state of Th1 cell activation, IL-10 secretion is induced more rapidly from recently activated than from resting cells. These findings indicate that IL-10 production by CD4+ T lymphocytes need not involve a distinct regulatory Th cell subset but can be generated in Th1 cells as part of the effector response to intracellular pathogens. 10.1084/jem.20062175 KW - il-10-tcells AU - Jankovic, Dragana AU - Kullberg, Marika AU - Feng, Carl AU - Goldszmid, Romina AU - Collazo, Carmen AU - Wilson, Mark AU - Wynn, Thomas AU - Kamanaka, Masahito AU - Flavell, Richard AU - Sher, Alan PY - 2007/02/19/ UR - http://dx.doi.org/10.1084/jem.20062175 ER -