Immune Responses to Retinal Self-Antigens in CD25+CD4+Regulatory T-Cell–Depleted Mice

Based on diverse activities and production of several cytokines, T lymphocytes and T helper cells are divided into Th1, Th2, Th17 and regulatory T-cell (T regs) subsets based on diverse activities and production of several cytokines. Infectious agents can escape from host by modulation of immune responses as effector T-cells and Tregs. Thus, regulatory T-cells play a critical role in suppression of immune responses to infectious agents such as viruses, bacteria, parasites and fungi and as well as preserving immune homeostasis. However, regulatory T-cell responses can advantageous for the body by minimizing the tissue-damaging effects. The following subsets of regulatory T-cells have been recognized: natural regulatory Tcells, Th3, Tr1, CD8+ Treg, natural killer like Treg (NKTreg) cells. Among various markers of Treg cells, Forkhead family transcription factor (FOXP3) as an intracellular protein is used for discrimination between activated T reg cells and activated T-cells. FOXP3 has a central role in production, thymocyte differentiation and function of regulatory Tcells. Several mechanisms have been indicated in regulation of T reg cells. As, the suppression of T-cells via regulatory T-cells is either mediated by Cell-cell contact and Immunosuppressive cytokines (TGF-Beta, IL-10) mediated.

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C-type lectins on dendritic cells: key modulators for the induction of immune responses

Biochemical Society Transactions ◽

10.1042/bst0361478 ◽

2008 ◽

Vol 36 (6) ◽

pp. 1478-1481 ◽

Cited By ~ 97

Author(s):

Yvette van Kooyk

Keyword(s):

Dendritic Cells ◽

T Cell ◽

Immune Responses ◽

Cell Polarization ◽

Cellular Interactions ◽

Antigen Receptors ◽

Lectin Receptors ◽

Signalling Molecules ◽

Intracellular Adhesion Molecule ◽

Self Antigens

DCs (dendritic cells) are specialized in the recognition of pathogens and play a pivotal role in the control of immune responses. DCs are also important for homoeostatic control, recognizing self-antigens and tolerizing the tissue environment. The nature of the antigen recognized tilts the balance towards immunity or tolerance. CLRs (C-type lectin receptors) expressed by DC are involved in the recognition and capture of many glycosylated self-antigens and pathogens. It is now becoming clear that these CLRs may not only serve as antigen receptors allowing internalization and antigen presentation, but also function in the recognition of glycosylated self-antigens, and as adhesion and/or signalling molecules. The expression of C-type lectins is very sensitive to maturation stimuli, leading to down-regulation as DCs mature. CLRs such as DC-SIGN (DC-specific intracellular adhesion molecule-3 grabbing non-integrin) recognizes high-mannose-containing structures and Lewis antigens (Lex, Ley, Leb and Lea), whereas the CLR MGL (macrophage galactose/N-acetylgalactosamine-specific C-type lectin) recognizes GalNAc. Lex, Ley and GalNAc glycan structures are often expressed on tumours. We have demonstrated that glycan modification of antigen can strongly enhance MHC class I responses and the induction of antigen-specific cytotoxic T-lymphocytes, indicating that glycosylated antigen targets C-type lectin to enhance antigen-specific T-cell responses. Moreover, these CLRs induce signalling processes in DCs and specific cytokine responses in combination with TLR (Toll-like receptor) triggering. This implies that specific C-type lectin-targeted antigens can regulate T-cell polarization. Understanding the diversity of C-type lectins being expressed on DCs as well as their carbohydrate-specific recognition profiles should promote understanding of pathogen recognition in many diseases, as well as the regulation of cellular interactions of DCs that are essential in the control of immunity.

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Immune Responses to Tissue-Restricted Self Antigens: Studies on T Cell Tolerance and Autoimmunity to Pancreatic Beta Cells

Current Topics in Microbiology and Immunology - Human Diabetes ◽

10.1007/978-3-642-75741-9_5 ◽

1990 ◽

pp. 71-94 ◽

Cited By ~ 2

Author(s):

D. Lo

Keyword(s):

T Cell ◽

Immune Responses ◽

Beta Cells ◽

Pancreatic Beta Cells ◽

T Cell Tolerance ◽

Cell Tolerance ◽

Self Antigens

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Adjuvant facilitates tolerance induction to factor VIII in hemophilic mice through a Foxp3-independent mechanism that relies on IL-10

Blood ◽

10.1182/blood-2012-09-457135 ◽

2013 ◽

Vol 121 (19) ◽

pp. 3936-3945 ◽

Cited By ~ 10

Author(s):

Vanessa G. Oliveira ◽

Ana Agua-Doce ◽

Maria A. Curotto de Lafaille ◽

Juan J. Lafaille ◽

Luis Graca

Keyword(s):

T Cell ◽

Immune Responses ◽

Factor Viii ◽

Regulatory T Cell ◽

Tolerance Induction ◽

Key Points ◽

Independent Mechanism

Key Points An adjuvant (alum), known to boost immune responses, can be used to facilitate a tolerogenic protocol. Nondepleting anti-CD4 can lead to Foxp3+ regulatory T-cell–independent tolerance that relies on IL-10.

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Genetic Immunization Maps T Cell (Auto)Immune Responses to Self Antigens Homologous to Exogenous Proteins

Autoimmunity ◽

10.1080/08916930290016592 ◽

2002 ◽

Vol 35 (2) ◽

pp. 105-110 ◽

Cited By ~ 1

Author(s):

Antonio La Cava ◽

Margherita Massa ◽

Alberto Mendivil ◽

Alberto Martini ◽

Salvatore Albani

Keyword(s):

T Cell ◽

Immune Responses ◽

Genetic Immunization ◽

Self Antigens

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Application of IgG-Derived Natural Treg Epitopes (IgG Tregitopes) to Antigen-Specific Tolerance Induction in a Murine Model of Type 1 Diabetes

Journal of Diabetes Research ◽

10.1155/2013/621693 ◽

2013 ◽

Vol 2013 ◽

pp. 1-17 ◽

Cited By ~ 23

Author(s):

Leslie P. Cousens ◽

Yan Su ◽

Elizabeth McClaine ◽

Xin Li ◽

Frances Terry ◽

...

Keyword(s):

T Cells ◽

Type 1 Diabetes ◽

T Cell ◽

Immune Responses ◽

Murine Model ◽

Regulatory T Cell ◽

Mononuclear Cells ◽

Ex Vivo ◽

The Impact

HLA class II-restricted regulatory T cell (Treg) epitopes in IgG (also called “Tregitopes”) have been reported to suppress immune responses to coadministered antigens by stimulating the expansion of natural Tregs (nTregs). Here we evaluate their impact on human immune responses to islet cell antigensex vivoand on the modulation of type 1 diabetes (T1D) in a murine modelin vivo. Co-administration of Tregitopes and T1D antigens delayed development of hyperglycemia and reduced the incidence of diabetes in NOD mice. Suppression of diabetes could be observed even following onset of disease. To measure the impact of Tregitope treatment on T cell responses, we evaluated the effect of Tregitope treatment in DO11.10 mice. Upregulation of FoxP3 in KJ1-26-stained OVA-specific CD4+T cells was observed following treatment of DO11.10 mice with Tregitopes, along with reductions in anti-OVA Ig and T effector responses. Inex vivostudies of human T cells, peripheral blood mononuclear cells’ (PBMC) responses to GAD65 epitopes in the presence and absence of Tregitope were variable. Suppression of immune responses to GAD65 epitopesex vivoby Tregitope appeared to be more effective in assays using PBMC from a newly diagnosed diabetic subject than for other more established diabetic subjects, and correlation of the degree of suppression with predicted HLA restriction of the Tregitopes was confirmed. Implementation of these defined regulatory T cell epitopes for therapy of T1D and other autoimmune diseases may lead to a paradigm shift in disease management.

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