The Role of T Cells in Type 1 Diabetes

The role of T cells as pathogenic effector cells in type 1 diabetes (T1D) is well established. Both CD4+ and CD8+ cells can play distinct and highly pathogenic roles mediating diabetogenesis. Other cell types including NK, B cells, macrophages and dendritic cells also play coordinate roles. Ultimately auto-aggressive T cells invade pancreatic islets focusing destructive force on the beta cells that produce insulin. The initial insult may be solely inflammation but nonetheless results in loss of insulin production. This chapter will focus on the different T cell subtypes including a newly described helper T cell subtype, Th40, which is highly pathogenic in T1D. Discussion will include how auto-aggressive T cells can arise and suggest alternative means to control auto-aggressive T cells. The ultimate goal for a successful treatment is to control pathogenic effector cells without causing immune suppression, a feat that has yet to be achieved. Considering new paradigms about diabetogenesis may provide substantive clues towards effectively curing this ravaging disease.

• Publication year

  2011

• Venue

  Unknown venue

• Publication date

  2011-11-25

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.5772/22040
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar

• No claims are published for this paper.

• No concepts are published for this paper.

• The Expanding Role of TNF-Receptor Super Family Member CD40 (tnfrsf5) in Autoimmune Disease: Focus on Th40 Cells

  2010cited by this paper
• Association of adiponectin, interleukin (IL)‐1ra, inducible protein 10, IL‐6 and number of islet autoantibodies with progression patterns of type 1 diabetes the first year after diagnosis

  2010cited by this paper
• HLA-E-restricted regulatory CD8(+) T cells are involved in development and control of human autoimmune type 1 diabetes.

  2010cited by this paper
• CD40 glycoforms and TNF-receptors 1 and 2 in the formation of CD40 receptor(s) in autoimmunity.

  2010cited by this paper
• IL-17 and Th17 Cells.

  2009cited by this paper
• Highly purified Th17 cells from BDC2.5NOD mice convert into Th1-like cells in NOD/SCID recipient mice.

  2009cited by this paper
• Functional plasticity of macrophages: in situ reprogramming of tumor‐associated macrophages

  2009influential reference
• Autoimmune diabetic patients undergoing allogeneic islet transplantation: are we ready for a regulatory T-cell therapy?

  2009cited by this paper
• Development and characterization of IL-21–producing CD4+ T cells

  2008cited by this paper
• Either a Th17 or a Th1 effector response can drive autoimmunity: conditions of disease induction affect dominant effector category

  2008cited by this paper
• Innocuous IFNγ induced by adjuvant-free antigen restores normoglycemia in NOD mice through inhibition of IL-17 production

  2008cited by this paper
• A rush to judgment on Th17

  2008cited by this paper
• Disruption of the homeostatic balance between autoaggressive (CD4+CD40+) and regulatory (CD4+CD25+FoxP3+) T cells promotes diabetes

  2008influential reference
• IL-17 and the Th17 lineage in systemic lupus erythematosus

  2008cited by this paper
• An analytical workflow for investigating cytokine profiles

  2008cited by this paper
• CD40 on NOD CD4 T cells contributes to their activation and pathogenicity.

  2008cited by this paper
• High Distribution of CD40 and TRAF2 in Th40 T Cell Rafts Leads to Preferential Survival of this Auto-Aggressive Population in Autoimmunity

  2008influential reference
• The Effector T Cells of Diabetic Subjects Are Resistant to Regulation via CD4+FOXP3+ Regulatory T Cells1

  2008cited by this paper
• IL-17A is produced by Th17, gammadelta T cells and other CD4- lymphocytes during infection with Salmonella enterica serovar Enteritidis and has a mild effect in bacterial clearance.

  2008cited by this paper
• Regulatory T cells and immune tolerance.

  2008cited by this paper
• Control of immune responses by antigen-specific regulatory T cells expressing the folate receptor.

  2007cited by this paper
• Age-dependent TCR revision mediated by interaction between alphabeta TCR and self-antigens.

  2007cited by this paper
• Cutting Edge: TCR Revision Affects Predominantly Foxp3− Cells and Skews Them toward the Th17 Lineage1

  2007cited by this paper
• A unique T cell subset described as CD4loCD40+ T cells (TCD40) in human type 1 diabetes.

  2007influential reference
• Age-Dependent TCR Revision Mediated by Interaction between αβ TCR and Self-Antigens

  2007cited by this paper
• Re-shaping the T cell repertoire: TCR editing and TCR revision for good and for bad.

  2007cited by this paper
• Th17: an effector CD4 T cell lineage with regulatory T cell ties.

  2006cited by this paper
• Interleukin-6 modulates production of T lymphocyte-derived cytokines in antigen-induced arthritis and drives inflammation-induced osteoclastogenesis.

  2006cited by this paper
• Multimeric Soluble CD40 Ligand and GITR Ligand as Adjuvants for Human Immunodeficiency Virus DNA Vaccines

  2006influential reference
• Foxp3+CD25+CD4+ natural regulatory T cells in dominant self‐tolerance and autoimmune disease

  2006cited by this paper
• A Costimulatory Function for T Cell CD40

  2006cited by this paper
• Th1 and Th2 lymphocytes in autoimmune disease.

  2005cited by this paper
• Revision of T cell receptor {alpha} chain genes is required for normal T lymphocyte development.

  2005cited by this paper
• Revision of T cell receptor α chain genes is required for normal T lymphocyte development

  2005cited by this paper
• The Role of CD40–CD154 Interactions in Autoimmunity and the Benefit of Disrupting this Pathway

  2004cited by this paper
• Peripheral CD4loCD40+ auto‐aggressive T cell expansion during insulin‐dependent diabetes mellitus

  2004cited by this paper
• Recombination activating genes (RAG) induce secondary Ig gene rearrangement in and subsequent apoptosis of human peripheral blood circulating B lymphocytes

  2004cited by this paper
• Cutting Edge: TCR Revision Occurs in Germinal Centers1

  2004cited by this paper
• Upregulation of CD40--CD40 ligand system in patients with diabetes mellitus.

  2004cited by this paper
• Expression of CD40 ligand on CD4+ T-cells and platelets correlated to the coronary artery lesion and disease progress in Kawasaki disease.

  2003cited by this paper
• Enhanced levels of CD154 (CD40 ligand) on platelets in patients with chronic heart failure

  2003cited by this paper
• Cutting Edge: CD40-Induced Expression of Recombination Activating Gene (RAG) 1 and RAG2: A Mechanism for the Generation of Autoaggressive T Cells in the Periphery1

  2003cited by this paper
• Differential Regulation of Peripheral CD4+ T Cell Tolerance Induced by Deletion and TCR Revision 1

  2003cited by this paper
• IL-12 Administration Accelerates Autoimmune Diabetes in Both Wild-Type and IFN-γ-Deficient Nonobese Diabetic Mice, Revealing Pathogenic and Protective Effects of IL-12-Induced IFN-γ1

  2003cited by this paper
• CD40/CD40L interaction is essential for the induction of EAE in the absence of CD28-mediated co-stimulation.

  2002cited by this paper
• Superantigen-Induced TCR α Locus Secondary Rearrangement: Role in Tolerance Induction1

  2002cited by this paper
• Superantigen-induced TCR alpha locus secondary rearrangement: role in tolerance induction.

  2002cited by this paper
• Platelet-derived CD40L: the switch-hitting player of cardiovascular disease.

  2002cited by this paper
• Expression of CD40 identifies a unique pathogenic T cell population in type 1 diabetes

  2002influential reference
• Platelet CD40 ligand (CD40L) – subcellular localization, regulation of expression, and inhibition by clopidogrel

  2001cited by this paper
• IFN-γ Affects Homing of Diabetogenic T Cells1

  2001cited by this paper
• T-cell subsets (Th1 versus Th2).

  2000cited by this paper
• Lymphocytes rearrange, edit and revise their antigen receptors to be useful yet safe.

  2000cited by this paper
• Receptor revision in peripheral T cells creates a diverse V beta repertoire.

  2000cited by this paper
• Receptor Revision in Peripheral T Cells Creates a Diverse Vβ Repertoire1

  2000cited by this paper
• TCR-mediated involvement of CD4+ transgenic T cells in spontaneous inflammatory bowel disease in lymphopenic mice.

  1999cited by this paper
• Requirement for CD154 in the progression of atherosclerosis

  1999cited by this paper
• Chronic modulation of the TCR repertoire in the lymphoid periphery.

  1999cited by this paper
• RAG reexpression and DNA recombination at T cell receptor loci in peripheral CD4+ T cells.

  1998cited by this paper
• The role of helper T cell subsets in autoimmune diseases.

  1998cited by this paper
• TCR transgenic mice in which usage of transgenic alpha- and beta-chains is highly dependent on the level of selecting ligand.

  1998cited by this paper
• TCR Transgenic Mice in Which Usage of Transgenic α- and β-Chains Is Highly Dependent on the Level of Selecting Ligand

  1998cited by this paper
• CD40 ligand-CD40 interactions are necessary for the initiation of insulitis and diabetes in nonobese diabetic mice.

  1997cited by this paper
• Functional CD40 ligand is expressed on human vascular endothelial cells, smooth muscle cells, and macrophages: implications for CD40-CD40 ligand signaling in atherosclerosis.

  1997cited by this paper
• The many roles of CD40 in cell-mediated inflammatory responses.

  1996cited by this paper
• Induction of autoimmunity in the absence of CD28 costimulation.

  1996cited by this paper
• The role of gp39 (CD40L) in immunity.

  1995cited by this paper
• T lymphocyte T cell-B cell-activating molecule/CD40-L molecules induce normal B cells or chronic lymphocytic leukemia B cells to express CD80 (B7/BB-1) and enhance their costimulatory activity.

  1994cited by this paper
• Prevention of collagen-induced arthritis with an antibody to gp39, the ligand for CD40.

  1993cited by this paper
• Essential role for interferon-gamma and interleukin-6 in autoimmune insulin-dependent diabetes in NOD/Wehi mice.

  1991cited by this paper
• EncephalomyelitisDevelopment of Experimental Autoimmune IL-17 Plays an Important Role in the

  year unknowncited by this paper

• Advances in our understanding of the pathophysiology of Type 1 diabetes: lessons from the NOD mouse.

  2014cites this paper