Virus-Induced Transient Immune Suppression and the Inhibition of T Cell Proliferation by Type I Interferon

Marshall, Heather D.; Urban, Stina L.; Welsh, Raymond M.

doi:10.1128/jvi.02516-10

Cited by 82 publications

(67 citation statements)

References 48 publications

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“…Like many other TLR ligands, poly(I:C) has routinely been used as an adjuvant, but others (33,34) and this study (Fig. 1) have shown that prior exposure to poly(I:C) can inhibit CD8 T-cell responses.…”

Section: Discussionmentioning

confidence: 60%

Presensitizing with a Toll-like receptor 3 ligand impairs CD8 T-cell effector differentiation and IL-33 responsiveness

Ngoi

Rose

Ménoret

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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The synthetic double-stranded RNA poly(I:C) is commonly used as an adjuvant to boost CD8 T-cell function; however, polyinosinic:polycytidylic acid [poly(I:C)] can also suppress autoimmune disease. The mechanism by which a single adjuvant achieves two distinct immunoregulatory roles is unknown. Although it is clear that coadministration of poly(I:C) with antigen elicits strong adjuvant effects in mice, we found that poly(I:C) injection before antigen substantially reduced antigen-dependent CD8 T-cell responses. Notably, CD8 T cells sensitized in poly(I:C)-pretreated mice failed to fully up-regulate IL-33R (ST2), which led to impaired T-cell receptor-independent responses to IL-33. In contrast, nonsensitized effector CD8 T cells responded robustly to IL-33 using a two-signal cytokine mechanism. During an acute lung response to Staphylococcus aureus enterotoxin, peripheral injection of poly(I:C) manifested a suppressive process by inhibiting the differentiation of both antigen- and IL-33–responsive CD8 effectors systemically. These findings highlight that early exposure to double-stranded RNA reverses its role as an adjuvant and, importantly, prevents IL-33R up-regulation on CD8 effector T cells to dampen inflammation.

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Section: Discussionmentioning

confidence: 60%

Presensitizing with a Toll-like receptor 3 ligand impairs CD8 T-cell effector differentiation and IL-33 responsiveness

Ngoi

Rose

Ménoret

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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“…However, cytokine production and migratory potential are only two aspects of a multifaceted T-cell response and the biological relevance of cytokines elicited by heterologous infection can also be ascertained by their influence on other parameters such as proliferation and cytolytic activity. Naïve T-cell proliferation may be inhibited by heterologous infection and/ or type I interferons (35), whereas LCMV-specific memory CD8 + T cells may undergo up to three rounds of proliferation in response to heterologous infection with vesicular stomatitis virus (36) and become actively cytolytic during heterologous vaccinia virus infection (37). Likewise, virus-specific CD4 + T cells initiate their proliferative program more rapidly when exposed to an inflammatory in vivo environment (38).…”

Section: Discussionmentioning

confidence: 99%

Regulation of innate CD8⁺T-cell activation mediated by cytokines

Freeman

Hammarlund

Raué

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

203

184

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Virus-specific CD8 + T cells develop the ability to function in an "innate" capacity by responding to a remarkable array of cytokines in a TCR-independent manner. Although several cytokines such as IL-12 and IL-18 have been identified as key regulators of CD8 + T-cell activation, the role of other cytokines and the ways in which they interact with each other remain unclear. Here, we have used an unbiased, systematic approach to examine the effects of 1,849 cytokine combinations on virus-specific CD8 + T-cell activation. This study identifies several unexpected cytokine combinations that synergize to induce antigen-independent IFNγ production and CD69 up-regulation by CD8 + T cells in addition to cytokines that exhibit differential regulatory functions, with the ability to either enhance or inhibit T-cell IFNγ production, depending on which cytokine partner is present. These findings underscore the complexity of cytokine interactions while also providing insight into the multifaceted regulatory network controlling virusspecific CD8 + T-cell functions.lymphocytic choriomeningitis virus | mouse | interleukin | lymphocyte

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“…65 A substantial loss in CD8 and CD4 T cell number during the first 5 days of LCMV infection parallels the levels of type 1 IFN production, does not occur in type 1 IFN receptor ko mice, 66 is blocked by antibody to type 1 IFN 67 and is mimicked by IFN-inducing toll receptor agonists, such as poly I:C. 66 The apoptotic loss of memory occurs prior to cell division. 63,66,68 An in silico virtual immune system model, IMMSIM, which unlike a biological system can selectively turn off either active or passive attrition, predicted that without the active attrition and apoptosis of memory T cells early in infection, crossreactive T cells might overwhelmingly dominate the response to an infection. 61,63 By selectively reducing the frequency of memory cells at the beginning of an immune response, there actually may develop a more diverse T cell response to a new pathogen, and that diversity may be beneficial to the host for control of the pathogen.…”

Section: Heterologous Immunity and T Cell Crossreactivitymentioning

confidence: 99%

Vaccination and heterologous immunity: educating the immune system

Gil¹,

Kenney²,

Mishra³

et al. 2015

Transactions of the Royal Society of Tropical Medicine and Hygiene

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This review discusses three inter-related topics: (1) the immaturity of the neonatal and infant immune response; (2) heterologous immunity, where prior infection history with unrelated pathogens alters disease outcome resulting in either enhanced protective immunity or increased immunopathology to new infections, and (3) epidemiological human vaccine studies that demonstrate vaccines can have beneficial or detrimental effects on subsequent unrelated infections. The results from the epidemiological and heterologous immunity studies suggest that the immune system has tremendous plasticity and that each new infection or vaccine that an individual is exposed to during a lifetime will potentially alter the dynamics of their immune system. It also suggests that each new infection or vaccine that an infant receives is not only perturbing the immune system but is educating the immune system and laying down the foundation for all subsequent responses. This leads to the question, is there an optimum way to educate the immune system? Should this be taken into consideration in our vaccination protocols?

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Virus-Induced Transient Immune Suppression and the Inhibition of T Cell Proliferation by Type I Interferon

Cited by 82 publications

References 48 publications

Presensitizing with a Toll-like receptor 3 ligand impairs CD8 T-cell effector differentiation and IL-33 responsiveness

Presensitizing with a Toll-like receptor 3 ligand impairs CD8 T-cell effector differentiation and IL-33 responsiveness

Regulation of innate CD8⁺T-cell activation mediated by cytokines

Vaccination and heterologous immunity: educating the immune system

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Virus-Induced Transient Immune Suppression and the Inhibition of T Cell Proliferation by Type I Interferon

Cited by 82 publications

References 48 publications

Presensitizing with a Toll-like receptor 3 ligand impairs CD8 T-cell effector differentiation and IL-33 responsiveness

Presensitizing with a Toll-like receptor 3 ligand impairs CD8 T-cell effector differentiation and IL-33 responsiveness

Regulation of innate CD8+T-cell activation mediated by cytokines

Vaccination and heterologous immunity: educating the immune system

Contact Info

Product

Resources

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Regulation of innate CD8⁺T-cell activation mediated by cytokines