Tumor necrosis factor alpha inhibits the suppressive effect of regulatory T cells on the hepatitis B virus–specific immune response

Stoop, Jeroen N.; Woltman, Andrea M.; Biesta, Paula J.; Kusters, Johannes G.; Kuipers, Ernst J.; Janssen, Harry L.A.; Molen, Renate G. van der

doi:10.1002/hep.21761

Cited by 49 publications

(33 citation statements)

References 36 publications

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“…Our results also do not reveal altered functions of CD4 + regulatory IL-10-producing T cells in the absence of p75-mediated signaling during LZT, which is in line with earlier work showing normal suppressive effects on T cell proliferation of regulatory CD4 + CD25 + T cells from p75-deficient mice (37). In contrast, other studies demonstrate that TNF induces a reduction or, in long term culture, an enhancement of number and function of naturally occurring CD4 + CD25 + regulatory T cells (12,(38)(39)(40)(41)(42).…”

Section: Discussionsupporting

confidence: 87%

T cell killing by tolerogenic dendritic cells protects mice from allergy

Luckey¹,

Maurer²,

Schmidt³

et al. 2011

J. Clin. Invest.

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It is well established that allergy development can be prevented by repeated low-dose exposure to contact allergens. Exactly which immune mechanisms are responsible for this so-called low zone tolerance (LZT) is not clear, although CD8 + suppressor T cells are known to have a role. Here, we show that TNF released by tolerogenic CD11 + CD8 + DCs located in skin-draining lymph nodes is required and sufficient for development of tolerance to contact allergens in mice. DC-derived TNF protected mice from contact allergy by inducing apoptosis in allergen-specific effector CD8 + T cells via TNF receptor 2 but did not contribute to the generation and function of the regulatory T cells associated with LZT. The TNF-mediated killing mechanism was induced in an allergen-specific manner. Activation of tolerogenic DCs by LZT CD8 + suppressor T cells and enhanced TNF receptor 2 expression on contact allergen-specific CD8 + effector T cells were required for LZT. Our findings may explain how tolerance protects from allergic diseases, which could allow for the development of new strategies for allergy prevention.

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Section: Discussionsupporting

confidence: 87%

T cell killing by tolerogenic dendritic cells protects mice from allergy

Luckey¹,

Maurer²,

Schmidt³

et al. 2011

J. Clin. Invest.

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“…Haplotype -318C?49G may lead to downregulation of CTLA-4 and thereby increased T cell response [25]. Because CTLA-4 engagement by B7-1 or B7-2 molecules plays a regulating role in the process of Th1/Th2 proliferation and differentiation in autoimmune disorders [17,22,23], CTLA4 gene polymorphism may lead to Th1/Th2 shift and imbalance. It is speculated that in chronic HBV infection, the composition of haplotypes from two loci affects cytokines.…”

Section: Discussionmentioning

confidence: 99%

“…Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), expressed on activated and regulatory T cells, regulates T cell activation and tolerance [14,15] as well as Th1/Th2 differentiation and cytokine production [16][17][18][19][20] upon B7 engagement. Cytokines such as TNF-a and IFN-c are critical for not only viral clearance but also immunopathogenesis of HBV infection [21][22][23][24]. Therefore, the interaction of CTLA-4 with B7 molecules in regulating T cell activation and Th1/Th2 cytokines production is involved in the immune response to HBV infection.…”

Section: Introductionmentioning

confidence: 99%

Associations between cytotoxic T lymphocyte-associated antigen-4 polymorphisms and serum tumor necrosis factor-α and interferon-γ levels in patients with chronic hepatitis B virus infection

et al. 2011

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“…Several theories exist regarding how TNF inhibitors reactivate hepatitis B. Elevated TNF levels are seen in both the serum and hepatocytes of patients with chronic hepatitis B [26], and are secreted by HBV-specific CTL [27]. TNF has biological activity and an amino acid sequence similar to lymphotoxin, which inhibits HBV replication [28]. Infected cells are also reported to be selectively killed by TNF [33].…”

Section: Resultsmentioning

confidence: 99%