Although interferon γ (IFN-γ) 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-γ effector functions. We analyzed the source of regulatory IL-10 in mice infected with the protozoan parasite Toxoplasma gondii. Unexpectedly, IFN-γ–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-γγ 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-γ, IL-10 production could be stimulated in IL-10−IFN-γ+ cells by further activation in vitro. In addition, experiments with T. gondii–specific IL-10+IFN-γ+ CD4 clones revealed that although IFN-γ 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.

ABSTRACT. In recent years, there has been a tremendous expansion in medical and dental research concerned with free radicals, reactive oxygen species, and anti-oxidant defense mechanisms. This review is intended to provide a critical, up-to-date summary of the field, with particular emphasis on its implications for the application of "anti-oxidant therapy" in periodontal disease. We have reviewed the nomenclature, mechanisms of actions, features, and sources of most common free radicals and reactive oxygen species, as well as analyzed the typical biological targets for oxidative damage. Based on a review of direct and indirect anti-oxidant host defenses, particularly in relation to the key role of polymorphonuclear neutrophils in periodontitis, we review current evidence for oxidative damage in chronic inflammatory periodontal disease, and the possible therapeutic effects of anti-oxidants in treating and/or preventing such pathology, with special attention to vitamin E and Co-enzyme Q.

Most cases of coccidioidomycosis in organ transplant recipients arise from either primary infection with Coccidioides immitis after environmental exposure or from reactivation of latent infection. Herein, we report 2 cases of rapidly fatal, disseminated coccidioidomycosis that occurred in organ transplant recipients who had never lived in or visited an area where C. immitis is endemic. Both subjects had received a transplanted organ from the same donor, an individual with unrecognized active coccidioidomycosis at the time of his death.