Dominance of IL-12 Over IL-4 in γδ T Cell Differentiation Leads to Default Production of IFN-γ: Failure to Down-Regulate IL-12 Receptor β2-Chain Expression

Yin, Zhinan; Zhang, Dong Hong; Welte, Thomas; Bahtiyar, Gül; Jung, Sung‐Soo; Liu, Lanzhen; Fu, Xin; Ray, Anuradha; Craft, Joe

doi:10.4049/jimmunol.164.6.3056

Cited by 82 publications

(87 citation statements)

References 59 publications

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“…To assess T cell cytokine production, splenocytes (2 ϫ 10 6 /ml) were activated with anti-CD3 and anti-CD28 in the presence of brefeldin A for 6 h, and cells were washed, fixed, permeabilized, and stained with FITC-anti-IFN-␥ and PE-anti-IL-4 or PE-anti-IL-10 (see genotypic analysis of cohorts above) as described (25). Meanwhile, cells were stained with CyChrome-anti-CD4 or anti-CD8 and biotin-B220 followed with avidinallophycocyanin.…”

Section: Intracellular Cytokine Stainingmentioning

confidence: 99%

IL-10 Regulates Murine Lupus

Yin

Bahtiyar

Zhang

et al. 2002

The Journal of Immunology

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210

175

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MRL/MpJ-Tnfrsf6lpr (MRL/MpJ-Faslpr; MRL-Faslpr) mice develop a spontaneous lupus syndrome closely resembling human systemic lupus erythematosus. To define the role of IL-10 in the regulation of murine lupus, IL-10 gene-deficient (IL-10−/−) MRL-Faslpr (MRL-Faslpr IL-10−/−) mice were generated and their disease phenotype was compared with littermates with one or two copies of an intact IL-10 locus (MRL-Faslpr IL-10+/− and MRL-Faslpr IL-10+/+ mice, respectively). MRL-Faslpr IL-10−/− mice developed severe lupus, with earlier appearance of skin lesions, increased lymphadenopathy, more severe glomerulonephritis, and higher mortality than their IL-10-intact littermate controls. The increased severity of lupus in MRL-Faslpr IL-10−/− mice was closely associated with enhanced IFN-γ production by both CD4+ and CD8+ cells and increased serum concentration of IgG2a anti-dsDNA autoantibodies. The protective effect of IL-10 in this lupus model was further supported by the observation that administration of rIL-10 reduced IgG2a anti-dsDNA autoantibody production in wild-type MRL-Faslpr animals. In summary, our results provide evidence that IL-10 can down-modulate murine lupus through inhibition of pathogenic Th1 cytokine responses. Modulation of the level of IL-10 may be of potential therapeutic benefit for human lupus.

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Section: Intracellular Cytokine Stainingmentioning

confidence: 99%

IL-10 Regulates Murine Lupus

Yin

Bahtiyar

Zhang

et al. 2002

The Journal of Immunology

Self Cite

210

175

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“…␥␦ T cells are CD8 ϩ and express either CD8␣␤ heterodimers or CD8␣␣ homodimers (68) and produce IFN-␥ preferentially (69). It should be noted that ␥␦ T cells, with or without CD8␣␣ homodimers, and ␣␤ T cells with CD8␣␣ homodimers are expressed in small intestine, but not in colon (70), which did not express elevated levels of IFN-␥ mRNA.…”

Section: Fig 10 Cytokine Profile Of Nhe3mentioning

confidence: 99%

In Vivo Evidence for Interferon-γ-mediated Homeostatic Mechanisms in Small Intestine of the NHE3 Na+/H+ Exchanger Knockout Model of Congenital Diarrhea

Woo¹,

Gildea²,

Tack³

et al. 2002

Journal of Biological Chemistry

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Mice lacking NHE3, the major absorptive Na ؉ /H ؉ exchanger in the intestine, are the only animal model of congenital diarrhea. To identify molecular changes underlying compensatory mechanisms activated in chronic diarrheas, cDNA microarrays and Northern blot analyses were used to compare global mRNA expression patterns in small intestine of NHE3-deficient and wildtype mice. Among the genes identified were members of the RegIII family of growth factors, which may contribute to the increased absorptive area, and a large number of interferon-␥-responsive genes. The latter finding is of particular interest, since interferon-␥ has been shown to regulate ion transporter activities in intestinal epithelial cells. Serum interferon-␥ was elevated 5-fold in NHE3-deficient mice; however, there was no evidence of inflammation, and unlike conditions such as inflammatory bowel disease, levels of other cytokines were unchanged. In addition, quantitative PCR analysis showed that up-regulation of interferon-␥ mRNA was localized to the small intestine and did not occur in the colon, spleen, or kidney. These in vivo data suggest that elevated interferon-␥, produced by gut-associated lymphoid tissue in the small intestine, is part of a homeostatic mechanism that is activated in response to the intestinal absorptive defect in order to regulate the fluidity of the intestinal tract.

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“…IFN-␥ is known to be a major product of ␥␦ T cells (30) and has multiple antiviral effects. Therefore, we examined the functional capacity of ␥␦ T cells in response to WN virus infection by first specifically quantifying their capability to produce IFN-␥.…”

Section: ␥␦ T Cells Provide Partial Protection By Producing Ifn-␥mentioning

confidence: 99%

IFN-γ-Producing γδ T Cells Help Control Murine West Nile Virus Infection

Wang

Scully

Yin

et al. 2003

The Journal of Immunology

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169

187

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West Nile (WN) virus causes fatal meningoencephalitis in laboratory mice, thereby partially mimicking human disease. Using this model, we have demonstrated that mice deficient in γδ T cells are more susceptible to WN virus infection. TCRδ−/− mice have elevated viral loads and greater dissemination of the pathogen to the CNS. In wild-type mice, γδ T cells expanded significantly during WN virus infection, produced IFN-γ in ex vivo assays, and enhanced perforin expression by splenic T cells. Adoptive transfer of γδ T cells to TCRδ−/− mice reduced the susceptibility of these mice to WN virus, and this effect was primarily due to IFN-γ-producing γδ T cells. These data demonstrate a distinct role for γδ T cells in the control of and prevention of mortality from murine WN virus infection.

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Dominance of IL-12 Over IL-4 in γδ T Cell Differentiation Leads to Default Production of IFN-γ: Failure to Down-Regulate IL-12 Receptor β2-Chain Expression

Cited by 82 publications

References 59 publications

IL-10 Regulates Murine Lupus

IL-10 Regulates Murine Lupus

In Vivo Evidence for Interferon-γ-mediated Homeostatic Mechanisms in Small Intestine of the NHE3 Na+/H+ Exchanger Knockout Model of Congenital Diarrhea

IFN-γ-Producing γδ T Cells Help Control Murine West Nile Virus Infection

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