دورية أكاديمية
أعرض في EDS

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

التفاصيل البيبلوغرافية
العنوان: Differential regulation of effector- and central-memory responses to Toxoplasma gondii Infection by IL-12 revealed by tracking of Tgd057-specific CD8+ T cells.
المؤلفون: Wilson DC; Center for Immunity and Inflammation, UMDNJ-New Jersey Medical School, Newark, New Jersey, United States of America., Grotenbreg GM, Liu K, Zhao Y, Frickel EM, Gubbels MJ, Ploegh HL, Yap GS
المصدر: PLoS pathogens [PLoS Pathog] 2010 Mar 19; Vol. 6 (3), pp. e1000815. Date of Electronic Publication: 2010 Mar 19.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Public Library of Science Country of Publication: United States NLM ID: 101238921 Publication Model: Electronic Cited Medium: Internet ISSN: 1553-7374 (Electronic) Linking ISSN: 15537366 NLM ISO Abbreviation: PLoS Pathog Subsets: MEDLINE
أسماء مطبوعة: Original Publication: San Francisco, CA : Public Library of Science, c2005-
مواضيع طبية MeSH: CD8-Positive T-Lymphocytes/*immunology , CD8-Positive T-Lymphocytes/*parasitology , Immunologic Memory/*immunology , Interleukin-12/*immunology , Toxoplasma/*immunology , Toxoplasmosis, Animal/*immunology, Animals ; Antigens, Protozoan/immunology ; Cell Differentiation/immunology ; Epitopes ; Immunophenotyping ; Interleukin-12/genetics ; Interleukin-12/metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Mutant Strains ; Signal Transduction/immunology
مستخلص: Production of the pro-inflammatory cytokine IL-12 by innate phagocytes drives the differentiation of IFN-gamma-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-2K(b)-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-gamma 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-gamma recall responses. Importantly, isolated CD62L(hi) KLRG1- CD8+ T cells differentiated in the absence of IL-12 were enhanced in their ability to generate IFN-gamma-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.
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معلومات مُعتمدة: R01 AI083405 United States AI NIAID NIH HHS; R56 AI083405 United States AI NIAID NIH HHS; R01 AI-83405 United States AI NIAID NIH HHS; R01 A150618 United States PHS HHS
المشرفين على المادة: 0 (Antigens, Protozoan)
0 (Epitopes)
187348-17-0 (Interleukin-12)
تواريخ الأحداث: Date Created: 20100325 Date Completed: 20100624 Latest Revision: 20211020
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC2841619
DOI: 10.1371/journal.ppat.1000815
PMID: 20333242
قاعدة البيانات: MEDLINE
الوصف
تدمد:1553-7374
DOI:10.1371/journal.ppat.1000815