The First Molecular Basis of the “Missing Self” Hypothesis

Borrego, Francisco

doi:10.4049/jimmunol.177.9.5759

Cited by 13 publications

(10 citation statements)

References 19 publications

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“…NK cells operate through the missing self hypothesis where lack of MHC antigen presentation on a target cell leads to activation of the NK cells and resultant cytotoxicity 22 . In an organ that was once considered immune-privileged, it is difficult to rationalize the presence of NK cells.…”

Section: Cell Types Contributing To Il-10 Production At the Maternal-mentioning

confidence: 99%

REVIEW ARTICLE: Interleukin‐10: A Multi‐Faceted Agent of Pregnancy

Thaxton

Sharma

2010

American J Rep Immunol

215

157

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It is widely accepted that pregnancy constitutes a unique developmental event. Unprecedented intrauterine actions of angiogenesis, immunity, and neuroendocrine regulation are juxtaposed to mechanisms of senescence that enable fetal growth and protection. The suppressive and regulatory factors that facilitate healthy pregnancy are under investigation. In non-pregnant systems of infection and inflammation the cytokine interleukin-10 (IL-10) has been widely investigated due to its potential as a key immunosuppressant in response to a multitude of inflammatory events. In the context of pregnancy, IL-10 levels increase markedly in women during early pregnancy and remain elevated well into the third trimester immediately prior to onset of labor. The role of IL-10 during pregnancy as a suppressor of active maternal immunity to allow acceptance of the fetal allograft has been a point of study. Moreover, secretion of IL-10 by a diverse set of maternal and fetal cells has proven to aid in the orchestration of normal processes of pregnancy. Interestingly, some of the more profound findings regarding the actions of IL-10 during pregnancy have manifested from research that focuses on aberrant pregnancy outcomes as a result of inflammation, hormonal imbalances, or gene-environment interactions. This review focuses on the role of IL-10 as a facilitator of successful pregnancy both as an immune suppressive agent and mediator of cross-talk between the placenta and the decidua. Importantly, we utilize investigations into adverse pregnancy conditions to further elucidate the multifarious role of IL-10 at the maternal-fetal interface.

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Section: Cell Types Contributing To Il-10 Production At the Maternal-mentioning

confidence: 99%

REVIEW ARTICLE: Interleukin‐10: A Multi‐Faceted Agent of Pregnancy

Thaxton

Sharma

2010

American J Rep Immunol

215

157

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“…The APC function of Mϕs and DCs may be compartmentalized, as DCs are present in the mucosa of the upper aerodigestive tract (UEDT) and serve to sample this microenvironment for antigenic stimuli,32 and Mϕs are commonly found in other solid organs. A third type of innate immune cell relevant to antitumor immunity is the NK cell, which can exhibit direct or indirect cytotoxic activity against cells with decreased MHC class I expression (the “missing self” hypothesis)35 or in the presence of other NK cell receptor ligands 36…”

Section: Discussionmentioning

confidence: 99%

The clinical implications of antitumor immunity in head and neck cancer

et al. 2011

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Recent developments have renewed interest in understanding the interaction between transformed cells and the immune system in the tumor microenvironment. Here, we provide a comprehensive review addressing the basics of tumor immunology in relation to head and neck cancer and the cellular components potentially involved in antitumor immune responses. In addition, we describe the mechanisms by which head and neck cancer cells escape immune-mediated killing and progress to form clinically significant disease. Further, we detail what effects standard anticancer therapies may have on antitumor immune responses and how these responses may be altered by current and investigational immunotherapies. Finally, we discuss future directions that need to be considered in the development of new immunotherapeutics designed to durably alter the immune response in favor of the host.

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“…NK cells then integrate inputs from additional activating and inhibitory stimuli to determine whether the cytotoxic threshold has been reached [75,76]. This mode of immune surveillance has led to the development of the missing-self hypothesis [77]. …”

Section: Natural Killer Cell-mediated Lysis Of Hpsc Derivativesmentioning

confidence: 99%

Immunogenicity of In Vitro Maintained and Matured Populations: Potential Barriers to Engraftment of Human Pluripotent Stem Cell Derivatives

Tang

Drukker

2013

Methods in Molecular Biology

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The potential to develop into any cell type makes human pluripotent stem cells (hPSCs) one of the most promising sources for regenerative treatments. Hurdles to their clinical applications include i) formation of heterogeneously differentiated cultures, ii) the risk of teratoma formation from residual undifferentiated cells, and iii) immune rejection of engrafted cells. The recent production of human isogenic (genetically identical) induced PSCs (hiPSCs) has been proposed as a “solution” to the histocompatibility barrier. In theory, differentiated cells derived from patient-specific hiPSC lines should be histocompatible to their donor/recipient. However, propagation, maintenance, and non-physiologic differentiation of hPSCs in vitro may produce other, likely less powerful, immune responses. In light of recent progress towards the clinical application of hPSCs, this review focuses on two antigen presentation phenomena that may lead to rejection of isogenic hPSC derivates: namely, the expression of aberrant antigens as a result of long-term in vitro maintenance conditions or incomplete somatic cell reprogramming, and the unbalanced presentation of receptors and ligands involved in immune recognition due to accelerated differentiation. Finally, we discuss immunosuppressive approaches that could potentially address these immunological concerns.

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The First Molecular Basis of the “Missing Self” Hypothesis

Cited by 13 publications

References 19 publications

REVIEW ARTICLE: Interleukin‐10: A Multi‐Faceted Agent of Pregnancy

REVIEW ARTICLE: Interleukin‐10: A Multi‐Faceted Agent of Pregnancy

The clinical implications of antitumor immunity in head and neck cancer

Immunogenicity of In Vitro Maintained and Matured Populations: Potential Barriers to Engraftment of Human Pluripotent Stem Cell Derivatives

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