Integrating immunity: The immunculus and self-reactivity

Poletaev, Alexander B.; Stepanyuk, Vladimir L.; Gershwin, M. Eric

doi:10.1016/j.jaut.2007.11.012

Cited by 64 publications

(43 citation statements)

References 47 publications

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“…Table 2 summarize characteristics that distinguishes between TaCD3 CD4+CD25 Treg, Tr-1 and Th3 cells. We note that this manuscript is part of a special series of papers on the mosaic of autoimmunity (28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38). Figure 1.…”

Section: Discussionmentioning

confidence: 99%

In vitro induction of regulatory T cells by anti-CD3 antibody in humans

Abraham

Karni

Dembinsky

et al. 2008

Journal of Autoimmunity

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Therapy with anti-CD3 antibody is effective in controlling models of autoimmune diseases and can reverse or prevent rejection of grafts. We studied the in vitro immunomodulatory effect of anti-CD3 treated human T cells. CD4 + T cells were stimulated with plate bound anti-CD3 and cultured for 12 days after which they were cultured with autologous peripheral blood mononuclear cells (PBMCs) and stimulated with soluble anti-CD3. We found that CD4 + T cells that were stimulated with anti-CD3 (T αCD3 ) markedly suppressed the proliferation and cytokine production of autologous PBMCs. These regulatory T cells were not induced by incubation with isotype control (T Control ) antibody or when anti-CD3 was combined with high doses of anti-CD28 (T αCD3/CD28 ). T αCD3 regulatory cells were anergic and produced lower levels of IFN-γ, TNF-α and IL-2, and higher levels of TGF-β than T Control or T αCD3/CD28 .There were no differences in the expression of CD25, CD45RB or CTLA-4 on T αCD3 as compared to T Control or T αCD3/CD28 and CD4 + CD25 − T αCD3 cells were identical to CD4 + CD25 + T αCD3 cells in their in vitro suppressive properties. Recombinant IL-2 in vitro abrogated the suppressive effect of T αCD3 . The suppressive effect was not related to apoptosis, was independent of HLA since T αCD3 also suppressed allogeneic PBMCs, and was not related to soluble factors. Finally, no suppression was observed when non T cells were removed from culture or when cultures were stimulated with plate bound anti-CD3, consistent with the ability of T αCD3 to downregulate CD80 on dendritic cells in co-culture experiments. Thus, we have identified human T cells with strong in vitro regulatory properties induced in vitro by anti-CD3 which appear to act in a non-HLA restricted fashion by affecting antigen presenting cells.

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Section: Discussionmentioning

confidence: 99%

In vitro induction of regulatory T cells by anti-CD3 antibody in humans

Abraham

Karni

Dembinsky

et al. 2008

Journal of Autoimmunity

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“…Indeed, autoimmunity is prominent in CVID [52,59,60,61] and 23–50% of patients manifest unclassified autoimmune features [28,62]. The mechanisms that lead to loss of tolerance in patients with immune deficiency as well as the same generic issue in autoimmune disease have been recently discussed [62,63,64,65,66,67,68,69,70,71,72]. In patients with X-linked agammaglobulinemia, a non-CVID disorder characterized by an extremely reduced B cell count, the remaining B cells are enriched in autoreactive clones [73].…”

Section: Cvid Clinical Featuresmentioning

confidence: 99%

Common Variable Immunodeficiency: Etiological and Treatment Issues

Deane

Selmi

Naguwa

et al. 2009

Int Arch Allergy Immunol

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One of the great advances in clinical medicine was the recognition of the pleomorphism of the immune response and the multiple afferent and efferent limbs of antigen processing and responsiveness. A significant contribution to this understanding was derived from studies of human immunodeficiency states, including both inherited and acquired syndromes. Amongst these syndromes, one of the most common, and least understood, is common variable immune deficiency (CVID). CVID is a syndrome that leads to a reduction in serum immunoglobulins and complications including recurrent infections. Management includes immunoglobulin replacement therapy; however, patients with CVID are at risk for complications of exogenous immunoglobulin administration as well as CVID-associated diseases such as autoimmune processes and malignancies. To assess the current state of knowledge in the field, we performed a literature review of a total of 753 publications covering the period of 1968 until 2008. From this list, 189 publications were selected for discussion. In this review, we demonstrate that while the molecular basis of CVID in many cases remains incompletely understood, significant strides have been made and it is now clear that there is involvement of several pathways of immune activation, with contributions from both T and B cells. Furthermore, despite the current gaps in our knowledge of the molecular pathogenesis of the syndrome, there have been dramatic advances in management that have led to improved survival and significantly reduced morbidity in affected patients.

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“…More than 50% of HCV-positive patients have symptoms of at least one EHM during the course of the disease that can be the first and only clinical signs of a chronic hepatitis C [2] . The loss of tolerance is the main mechanism that promotes autoimmune diseases and, particularly, autoimmune thyroid disorders (AITD) [3,4] , with autoantibodies (Abs) or T lymphocytes (humoral or cellular response) reacting with self-antigens (Ags) (Figure 1). …”

Section: Introductionmentioning

confidence: 99%

Hepatitis C virus infection and thyroid autoimmune disorders: A model of interactions between the host and the environment

Pastore¹

2016

WJH

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The hepatitis C virus (HCV) infection is an important public health problem and it is associated with hepatic and extrahepatic manifestations. Autoimmune thyroid diseases are common in HCV infected patients and the standard interferon-based treatment is associated with an increase of the immune-mediated thyroid damage. Recent evidence in the literature analyzed critical points of the mechanisms of thyroid damage, focusing on the balance between the two sides of the interaction: The environment (virus infection with potential crossreaction) and the host (susceptibility genes with consistent immune response). The spectrum of antiviral treatment for chronic HCV infection is rapidly expanding for the development of dual o triple therapy. The availability of interferon-free combined treatment with direct antiviral agents for HCV is very promising, in order to ameliorate the patient compliance and to reduce the development of thyroid autoimmunity.

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Integrating immunity: The immunculus and self-reactivity

Cited by 64 publications

References 47 publications

In vitro induction of regulatory T cells by anti-CD3 antibody in humans

In vitro induction of regulatory T cells by anti-CD3 antibody in humans

Common Variable Immunodeficiency: Etiological and Treatment Issues

Hepatitis C virus infection and thyroid autoimmune disorders: A model of interactions between the host and the environment

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