scholarly journals Paraneoplastic Autoimmunity in Thymus Tumors

1998 ◽  
Vol 6 (1-2) ◽  
pp. 129-140 ◽  
Author(s):  
Alexander Marx ◽  
Anja Schultz ◽  
Annette Wilisch ◽  
Markus Helmreich ◽  
Regina Nenninger ◽  
...  
Keyword(s):  
T Cells ◽  
Autoimmune Disease ◽  
Acetylcholine Receptor ◽  
Quantitative Difference ◽  
Human Tumor ◽  
Autoreactive T Cells ◽  
Thymic Epithelial Tumors ◽  
Functional Features ◽  
Paraneoplastic Autoimmunity ◽  
Autoimmune Phenomena

Autoimmune phenomena are more frequent in thymic epithelial tumors (TET) than in any other human tumor. Mysthenia gravis (MG) is by far the most common autoimmune disease in thymoma patients. MG is characterized by muscle weakness due to autoantibodies against the acetylcholine receptor (AChR), and CD4+AChR-specific T cells play a pivotal role for the production of these autoantibodies. About 10% of MG patients have a thymoma and, interestingly, only such thymomas exhibit an MG association that maintains thymuslike morphological and functional features with respect to the homing and differentiation of immature T cells. Since AChR protein is not expressed in thymomas, the specificity of the autoimmunity in thymoma-associated MG is thought to be determined by nonreceptor proteins with AChR epitopes. Such proteins are overexpressed in cortical-type MG-associated thymomas, and medullary thymomas express these proteins at barely detectable levels. Aside from this quantitative difference, the pathogenesis of anti-AChR autoimmunity might be qualitatively different in these thymoma subtypes. Our findings suggest that an antigen-specific abnormal Tcell selection by cortical-type TET may contribute to the pathogenesis of paraneoplastic MG. In contrast, an abnormal (intratumorous) activation of autoreactive T cells may be operative in medullary thymomas.

scholarly journals FOXP3 Defines Regulatory T Cells in Human Tumor and Autoimmune Disease

2009 ◽  
Vol 69 (9) ◽  
pp. 3995-4000 ◽  
Author(s):  
Ilona Kryczek ◽  
Rebecca Liu ◽  
Guobin Wang ◽  
Ke Wu ◽  
Xiaogong Shu ◽  
...  
Keyword(s):  
T Cells ◽  
Autoimmune Disease ◽  
Regulatory T Cells ◽  
Human Tumor

scholarly journals Expression of costimulatory molecules B7-1 (CD80), B7-2 (CD86), and interleukin 12 cytokine in multiple sclerosis lesions.

1995 ◽  
Vol 182 (6) ◽  
pp. 1985-1996 ◽  
Author(s):  
A Windhagen ◽  
J Newcombe ◽  
F Dangond ◽  
C Strand ◽  
M N Woodroofe ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
T Cell ◽  
Autoimmune Disease ◽  
T Cell Activation ◽  
Costimulatory Molecules ◽  
Interleukin 12 ◽  
Early Event ◽  
Time Duration ◽  
Autoreactive T Cells

Resting autoreactive T cells are present in the circulation of normal individuals without pathologic consequences. In autoimmune animal models, stimulation of these self-reactive T cells in the presence of costimulatory molecules B7-1 results in T cell-mediated autoimmune disease, whereas B7-2 stimulation generates regulatory autoreactive T cells that abrogate disease severity. Thus, reactivation in the brain of myelin-autoreactive T cells by antigen with costimulatory molecules may be a critical event in the pathophysiology of multiple sclerosis (MS), a putative autoimmune disease of central nervous system (CNS) myelin. We investigated the expression of cytokines and costimulatory molecules in a panel of 41 histologically characterized CNS specimens from 15 MS and 10 control cases using semiquantitative reverse transcriptase-polymerase chain reaction and immunocytochemistry. In four cases, vascular CNS infarcts with inflammation were compared with MS plaques from the same brain. We observed increased expression of B7-1 and interleukin (IL) 12p40 in acute MS plaques, particularly from early disease cases but not in inflammatory infarcts. B7-1 staining was localized predominantly to the lymphocytes in perivenular inflammatory cuffs but not the parenchyma. In contrast, B7-2 was expressed predominantly on macrophages both in MS lesions of varied time duration and in inflammatory infarcts. These findings indicate that an early event in the initiation of MS involves upregulation of B7-1 and IL-12, resulting in conditions that maximally stimulate T cell activation and induction of T helper 1-type immune responses.

Sa.19. Autoreactive T-Cells Mediate NK Cell Degeneration in Autoimmune Disease

2006 ◽  
Vol 119 ◽  
pp. S111
Author(s):  
Ruolan Liu ◽  
Luc Van Kaer ◽  
Antonio La Cava ◽  
Mary Price ◽  
Denise Campagnolo ◽  
...  
Keyword(s):  
T Cells ◽  
Autoimmune Disease ◽  
Nk Cell ◽  
Cell Degeneration ◽  
Autoreactive T Cells

scholarly journals Suppression of autoimmune disease after vaccination with autoreactive T cells that express Qa-1 peptide complexes

2004 ◽  
Vol 113 (8) ◽  
pp. 1218-1224 ◽  
Author(s):  
Vily Panoutsakopoulou ◽  
Katharina M. Huster ◽  
Nami McCarty ◽  
Evan Feinberg ◽  
Rijian Wang ◽  
...  
Keyword(s):  
T Cells ◽  
Autoimmune Disease ◽  
Autoreactive T Cells ◽  
Peptide Complexes

Subsets of CD4 + T cells and their roles in autoimmunity

1993 ◽  
Vol 342 (1299) ◽  
pp. 51-56 ◽  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Autoimmune Disease ◽  
Tissue Distribution ◽  
Cd4 T Cells ◽  
Essential Role ◽  
Autoreactive T Cells ◽  
Laboratory Rats ◽  
Self Tolerance ◽  
Peripheral T Cells

The CD4 molecule has a very restricted tissue distribution being found at high levels only on subpopulations of thymocytes and peripheral T cells. This finding implicated the molecule in the specialized actions of these cells and provided the impetus for studies directed at determining the function of the CD4 molecule itself and of those T cells that expressed it. The first part of this paper reviews briefly some of the earlier work in this field in which Alan Williams played such a major role. The paper concludes with an account of more recent findings which reveal that CD4 + T cells are themselves phenotypically heterogeneous and that the different subsets that can be identified mediate markedly different immunological functions. In particular studies with laboratory rats have shown that one subset plays an essential role in the prevention of autoimmunity. This finding indicates that self tolerance cannot be accounted for entirely in terms of the deletion or irreversible inactivation of autoreactive T cells and raises a number of questions about how the immune response to self antigens is actively regulated and how possible deficiencies in this regulation may give rise to autoimmune disease.

scholarly journals Narcolepsy type 1: what have we learned from immunology?

SLEEP ◽  
2020 ◽  
Vol 43 (10) ◽  
Author(s):  
Birgitte R Kornum
Keyword(s):  
T Cells ◽  
Autoimmune Disease ◽  
Adaptive Immune Response ◽  
Autoimmune Response ◽  
Healthy Individuals ◽  
Epidemiological Evidence ◽  
Autoreactive T Cells ◽  
Blood Samples ◽  
Adaptive Immune

Abstract Narcolepsy type 1 is hypothesized to be an autoimmune disease targeting the hypocretin/orexin neurons in the hypothalamus. Ample genetic and epidemiological evidence points in the direction of a pathogenesis involving the immune system, but this is not considered proof of autoimmunity. In fact, it remains a matter of debate how to prove that a given disease is indeed an autoimmune disease. In this review, a set of commonly used criteria for autoimmunity is described and applied to narcolepsy type 1. In favor of the autoimmune hypothesis are data showing that in narcolepsy type 1 a specific adaptive immune response is directed to hypocretin/orexin neurons. Autoreactive T cells and autoantibodies have been detected in blood samples from patients, but it remains to be seen if these T cells or antibodies are in fact present in the hypothalamus. It is also unclear if the autoreactive T cells and/or autoantibodies can transfer the disease to healthy individuals or animals or if immunization with the proposed autoantigens can induce the disease in animal models. Most importantly, it is still controversial whether suppression of the autoimmune response can prevent disease progression. In conclusion, narcolepsy type 1 does still not fully meet the criteria for being classified as a genuine autoimmune disease, but more and more results are pointing in that direction.

scholarly journals Studies in B7-Deficient Mice Reveal a Critical Role for B7 Costimulation in Both Induction and Effector Phases of Experimental Autoimmune Encephalomyelitis

1999 ◽  
Vol 190 (5) ◽  
pp. 733-740 ◽  
Author(s):  
Tammy T. Chang ◽  
Claudia Jabs ◽  
Raymond A. Sobel ◽  
Vijay K. Kuchroo ◽  
Arlene H. Sharpe
Keyword(s):  
T Cells ◽  
Autoimmune Disease ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Wild Type ◽  
Autoimmune Encephalomyelitis ◽  
Autoreactive T Cells ◽  
Effector Phase ◽  
Deficient Mice ◽  
Experimental Autoimmune

The importance of B7 costimulation in regulating T cell expansion and peripheral tolerance suggests that it may also play a significant regulatory role in the development of autoimmune disease. It is unclear whether B7 costimulation is involved only in the expansion of autoreactive T cells in the periphery, or if it is also required for effector activation of autoreactive T cells in the target organ for mediating tissue injury and propagating autoimmune disease. In this study, the role of B7–CD28 costimulation and the relative importance of B7 costimulators for the induction and effector phases of experimental autoimmune encephalomyelitis (EAE) induced by myelin oligodendrocyte glycoprotein (MOG) peptide were examined. Wild-type, B7-1/B7-2–deficient mice, or CD28-deficient C57BL/6 mice were immunized with MOG 35-55 peptide. Mice lacking both B7-1 and B7-2 or CD28 showed no or minimal clinical signs of EAE and markedly reduced inflammatory infiltrates in the brain and spinal cord. However, mice lacking either B7-1 or B7-2 alone developed clinical and pathologic EAE that was comparable to EAE in wild-type mice, indicating overlapping functions for B7-1 and B7-2. Resistance to EAE was not due to a lack of induction of T helper type 1 (Th1) cytokines, since T cells from B7-1/B7-2−/− mice show reduced proliferative responses, but greater interferon γ production compared with T cells from wild-type mice. To study the role of B7 molecules in the effector phase of the disease, MOG 35-55–specific T lines were adoptively transferred into the B7-1/B7-2−/− and wild-type mice. Clinical and histologic EAE were markedly reduced in B7-1/B7-2−/− compared with wild-type recipient mice. These results demonstrate that B7 costimulation has critical roles not only in the initial activation and expansion of MOG-reactive T cells, but also in the effector phase of encephalitogenic T cell activation within the central nervous system.

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