Interleukin 2 Activates BB/W Diabetic Rat Lymphoid Cells Cytotoxic to Islet Cells

Pukel, Clifford S.; Baquerizo, Hernan; Rabinovitch, Alex

doi:10.2337/diab.36.11.1217

Cited by 13 publications

(5 citation statements)

References 17 publications

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“…Previous studies also suggested that NK cells mediate islet cell lysis in vitro (19)(20)(21). Our study extended these observations with in vivo immune elimination of ASG^ cells and flow microfluorometric separation of CD8 + /CD5~ cells to demonstrate that NK effector cell populations from nondiabetic WF rats, nu/nu rats, and diabetic BB rats can all lyse islets in vitro.…”

Section: Discussionsupporting

confidence: 79%

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Intrinsic Cytotoxicity of Natural Killer Cells to Pancreatic Islets In Vitro

Nakamura

Ba²,

Tafuri³

et al. 1990

Diabetes

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BB rats develop spontaneous autoimmune insulin-dependent diabetes mellitus that is similar to human insulin-dependent diabetes. In this study, we used an in vitro islet cell cytotoxicity assay to study the possible role of natural killer (NK) cells and their soluble effector molecules in this disorder. First, the results demonstrated that in vivo treatment of acutely diabetic BB rats with anti-asialogangliosideM1 (an NK cell antiserum) but not with anti-T-lymphocyte antibodies reduces spleen cell cytotoxic activity to islets in vitro. Flow microfluorometry (FMF)-sorting experiments were then used to confirm that the splenic cytotoxic effector cell in acutely diabetic BB rats is a CD8+/CD5- NK cell. Further analysis demonstrated that both FMF-sorted NK cell populations from Wistar-Furth rats and unfractionated spleen cells from athymic nu/nu rats with high intrinsic NK cell activity also exhibit high islet cell cytotoxic activity in vitro. Finally, we found that the kinetics and differential cytotoxic activity of NK cells toward islets in vitro could be mimicked by NK cell culture supernatants containing high levels of NK cytotoxic factor (NKCF). The islet cytotoxic activity of these culture supernatants was specifically inhibited by the addition of anti-NKCF monoclonal antibody. These results demonstrate that NK cells from diabetic and nondiabetic rats are cytotoxic to islet cells in vitro. They further suggest that this cytotoxic effect may be mediated in part through the production and release of soluble factors such as NKCF.

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Section: Discussionsupporting

confidence: 79%

“…In vivo immune elimination of NK cells by administration of either anti-CD8 monoclonal antibody (MoAb) (6) or rabbit anti-asialoganglioside M1 (a-ASG M1 ) antiserum (17,18) prevents the disease. Furthermore, results of in vitro assays of islet cytotoxicity suggest that NK cells from the spleens of AD-BB rats lyse islet cells (19)(20)(21).…”

mentioning

confidence: 99%

Intrinsic Cytotoxicity of Natural Killer Cells to Pancreatic Islets In Vitro

Nakamura

Ba²,

Tafuri³

et al. 1990

Diabetes

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“…In addition to their antiviral activities resulting in reduction of permissiveness of cells to viral infection and replication described during CV-B infection of human pancreatic islet cells [30,115,[145][146][147][148][149], IFN-α and IFN-γ can also enhance NK cells cytolytic activity and upregulate HLA class I expression on islet endocrine cells [34,[150][151][152][153][154][155][156]. Thus, during enteroviral infection of genetically susceptible individuals, the possible activation of local NK cells by IFN-α in islets can be a primary cause leading to infected beta cells cytolysis, release of beta-cell antigens and hence activation of antigen-specific CD8 cytotoxic T cells, which is consistent with studies reporting that IFN-α expressed in insulin-producing beta cells can induce T1D in transgenic mice and that beta cells are especially sensitive to NK cell-mediated killing in BB/W diabetic and diabetes-prone rats [157][158][159].…”

Section: Possible Mechanisms Of Nk Cells Involvement In Cv-b-induced T1dsupporting

confidence: 86%

Enteroviral Pathogenesis of Type 1 Diabetes: The Role of Natural Killer Cells

Nekoua

Dechaumes²,

Sané³

et al. 2020

Microorganisms

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Enteroviruses, especially group B coxsackieviruses (CV-B), have been associated with the development of chronic diseases such as type 1 diabetes (T1D). The pathological mechanisms that trigger virus-induced autoimmunity against islet antigens in T1D are not fully elucidated. Animal and human studies suggest that NK cells response to CV-B infection play a crucial role in the enteroviral pathogenesis of T1D. Indeed, CV-B-infected cells can escape from cytotoxic T cells recognition and destruction by inhibition of cell surface expression of HLA class I antigen through non-structural viral proteins, but they can nevertheless be killed by NK cells. Cytolytic activity of NK cells towards pancreatic beta cells persistently-infected with CV-B has been reported and defective viral clearance by NK cells of patients with T1D has been suggested as a mechanism leading to persistence of CV-B and triggering autoimmunity reported in these patients. The knowledge about host antiviral defense against CV-B infection is not only crucial to understand the susceptibility to virus-induced T1D but could also contribute to the design of new preventive or therapeutic approaches for individuals at risk for T1D or newly diagnosed patients.

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“…NK cells lyse human cells that have not been infected with virus nor transformed [104, 134–136]. In the context of autoimmune disease, it is of interest that human oligodendrocytes are destroyed by peripheral blood‐derived mononuclear cell preparations enriched for NK cells [135, 136], and that rodent NK cells destroy autologous neurons [137] and pancreatic islet cells [138–141]. It is currently unknown whether a change in the expression of ligands (e.g.…”

Section: Autoimmune Diseasementioning

confidence: 99%

The Natural Killer Cell – Friend or Foe in Autoimmune Disease?

et al. 2002

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Autoimmune diseases are chronic conditions resulting from a loss of immunological tolerance to self‐antigens. Recent observations have supported an ever‐broader role for innate immune responses in directing and regulating adaptive immunity, including responses to self. This review summarizes recent findings supporting important functions of natural killer (NK) cells in regulating autoimmunity. A close survey of the current literature reveals multiple steps where NK cells can regulate inflammation and intervene in loss of self‐tolerance. Importantly, the findings also caution against inferring a similar role for NK cells in all autoimmune phenomena or during separate stages of the same disease. Indeed, NK cells may have different influences during the priming and the effector phases of disease. Hence, an increased understanding of the involvement of NK cells in inflammation and infection should provide new insights into the pathogenesis of autoimmune disease.

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Interleukin 2 Activates BB/W Diabetic Rat Lymphoid Cells Cytotoxic to Islet Cells

Cited by 13 publications

References 17 publications

Intrinsic Cytotoxicity of Natural Killer Cells to Pancreatic Islets In Vitro

Intrinsic Cytotoxicity of Natural Killer Cells to Pancreatic Islets In Vitro

Enteroviral Pathogenesis of Type 1 Diabetes: The Role of Natural Killer Cells

The Natural Killer Cell – Friend or Foe in Autoimmune Disease?

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