HIV and Autoimmunity

Zandman‐Goddard, Gisele; Shoenfeld, Yehuda

doi:10.1016/b978-044451271-0.50014-4

Cited by 47 publications

(59 citation statements)

References 44 publications

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“…Our studies focused entirely on human allogeneic stem cell transplantation as a model system for studying Treg homeostasis. Autoimmune diseases and treatment-related autoimmune syndromes are also often associated with lymphopenia (66)(67)(68)(69)(70)(71). In patients with cancer, infusions of autologous T cells specific for self-tumor-associated antigens appear to be more effective when administered to patients with lymphopenia (72,73).…”

Section: Discussionmentioning

confidence: 99%

Altered regulatory T cell homeostasis in patients with CD4+ lymphopenia following allogeneic hematopoietic stem cell transplantation

Matsuoka¹,

Kim²,

McDonough³

et al. 2010

J. Clin. Invest.

213

211

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CD4 + CD25 + Foxp3 + Tregs have an indispensable role in the maintenance of tolerance after allogeneic HSC transplantation (HSCT). Patients with chronic graft-versus-host disease (GVHD) have fewer circulating Tregs, but the mechanisms that lead to this deficiency of Tregs after HSCT are not known. Here, we analyzed reconstitution of Tregs and conventional CD4 + T cells (Tcons) in patients who underwent allogeneic HSCT after myeloablative conditioning. Following transplant, thymic generation of naive Tregs was markedly impaired, and reconstituting Tregs had a predominantly activated/memory phenotype. In response to CD4 + lymphopenia after HSCT, Tregs underwent higher levels of proliferation than Tcons, but Tregs undergoing homeostatic proliferation also showed increased susceptibility to Fas-mediated apoptosis. Prospective monitoring of CD4 + T cell subsets revealed that Tregs rapidly expanded and achieved normal levels by 9 months after HSCT, but Treg levels subsequently declined in patients with prolonged CD4 + lymphopenia. This resulted in a relative deficiency of Tregs, which was associated with a high incidence of extensive chronic GVHD. These studies indicate that CD4 + lymphopenia is a critical factor in Treg homeostasis and that prolonged imbalance of Treg homeostasis after HSCT can result in loss of tolerance and significant clinical disease manifestations.

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Section: Discussionmentioning

confidence: 99%

Altered regulatory T cell homeostasis in patients with CD4+ lymphopenia following allogeneic hematopoietic stem cell transplantation

Matsuoka¹,

Kim²,

McDonough³

et al. 2010

J. Clin. Invest.

213

211

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“…Autoimmunity characterized by the generation of autoAbs and the activation of autoreactive lymphocytes has been demonstrated in a number of viral infections, such as human immunodeficiency virus, hepatitis C virus, cytomegalovirus, herpes simplex virus and Epstein-Barr virus [26][27][28][29][30][31][32] . The generation of autoAbs cross-reactive with endothelial cells is involved in several autoimmune vascular diseases [33][34][35] .…”

Section: Discussionmentioning

confidence: 99%

C-Terminal Region of Dengue Virus Nonstructural Protein 1 Is Involved in Endothelial Cell Cross-Reactivity via Molecular Mimicry

Wan¹,

Lin²,

Chen³

et al. 2008

American J. of Infectious Diseases

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Infection with dengue virus (DV) causes diseases ranging from self-limited dengue fever to life-threatening dengue hemorrhagic fever and dengue shock syndrome. Vascular leakage, thrombocytopenia and bleeding are the clinical manifestations associated with dengue hemorrhage. We previously showed that anti-DV nonstructural protein 1 (NS1) antibodies (Abs) cross-reacted with endothelial cells. The potential target proteins on endothelial cell surface recognized by anti-DV NS1 Abs showed sequence homology with the C-terminal amino acids (a.a.) 311-352 of DV NS1. In this study, the role of NS1 C-terminal region in dengue autoimmunity was investigated. We deleted the a.a. 277-352 of DV NS1 to prepare truncated NS1 (tNS1) and generated anti-DV tNS1 Abs in mice. The endothelial cell-binding activity of anti-DV tNS1 Abs was lower than that of anti-DV NS1 Abs. In addition, the endothelial cell-binding activity of anti-DV NS1 Abs was inhibited by preabsorption with DV NS1 but not with DV tNS1 proteins. The anti-P311 (a.a. 311-330) and anti-P331 (a.a. 331-350) titers of dengue patient sera were positively correlated with their endothelial cell-binding activity. Dengue patient sera showed lower binding activity to DV tNS1 than to DV NS1 proteins. The endothelial cell-binding activity of dengue patient sera was inhibited by preabsorption with P311 and P331. This study helps to understand the molecular mechanisms of autoimmunity mediated by anti-DV NS1 Abs and to provide the potential implications of tNS1 in dengue vaccine strategies.

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“…If the theory is correct, then the more chronic, concurrent infections an individual develops, or the larger the number of distinct antigens encountered simultaneously (as in multiple vaccination programs for soldiers going overseas) the greater will be their probability of contracting a pair of complementary antigens that mimic one or more "self" determinants. People with AIDS are prototypes for this scenario and, indeed, they develop all forms of autoimmunity at hundreds of times the rate found in the general population (Morrow et al 1991, Zandman-Goddard andShoenfeld 2002). This fact suggests that studying the specific sets of infections that occur simultaneously in individual patients in terms of their subsequent development of autoimmune diseases may provide crucial clues to the origins of these diseases Hobbs 1992, Root-Bernstein andDeWitt 1994;RootBernstein 1995).…”

Section: Predictions Made By the Theorymentioning

confidence: 99%

Antigenic Complementarity in the Origins of Autoimmunity: A General Theory Illustrated With a Case Study of Idiopathic Thrombocytopenia Purpura

Root‐Bernstein

Couturier

2006

Journal of Immunology Research

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We describe a novel, testable theory of autoimmunity, outline novel predictions made by the theory, and illustrate its application to unravelling the possible causes of idiopathic thrombocytopenia purpura (ITP). Pairs of stereochemically complementary antigens induce complementary immune responses (antibody or T-cell) that create loss of regulation and civil war within the immune system itself. Antibodies attack antibodies creating circulating immune complexes; T-cells attack T-cells creating perivascular cuffing. This immunological civil war abrogates the self -nonself distinction. If at least one of the complementary antigens mimics a self antigen, then this unregulated immune response will target host tissues as well. Data demonstrating that complementary antigens are found in some animal models of autoimmunity and may be present in various human diseases, especially ITP, are reviewed. Specific mechanisms for preventing autoimmunity or suppressing existing autoimmunity are derived from the theory, and critical tests proposed. Finally, we argue that Koch's postulates are inadequate for establishing disease causation for multiple-antigen diseases and discuss the possibility that current research has failed to elucidate the causes of human autoimmune diseases because we are using the wrong criteria.

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HIV and Autoimmunity

Cited by 47 publications

References 44 publications

Altered regulatory T cell homeostasis in patients with CD4+ lymphopenia following allogeneic hematopoietic stem cell transplantation

Altered regulatory T cell homeostasis in patients with CD4+ lymphopenia following allogeneic hematopoietic stem cell transplantation

C-Terminal Region of Dengue Virus Nonstructural Protein 1 Is Involved in Endothelial Cell Cross-Reactivity via Molecular Mimicry

Antigenic Complementarity in the Origins of Autoimmunity: A General Theory Illustrated With a Case Study of Idiopathic Thrombocytopenia Purpura

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