scholarly journals Thymus and autoimmunity. Transplantation of the thymus from cyclosporin A-treated mice causes organ-specific autoimmune disease in athymic nude mice.

1988 ◽  
Vol 167 (4) ◽  
pp. 1479-1485 ◽  
Author(s):  
S Sakaguchi ◽  
N Sakaguchi
Keyword(s):  
T Cells ◽  
Autoimmune Disease ◽  
Autoimmune Diseases ◽  
Cyclosporin A ◽  
Spleen Cell ◽  
Nude Mice ◽  
Cell Suspensions ◽  
Suppressor T Cells ◽  
Athymic Nude Mice ◽  
Organ Specific

Organ-specific autoimmune diseases such as gastritis, oophoritis, thyroiditis, or insulitis developed in athymic nu/nu mice after engraftment of the thymus from euthymic nu/+ mice treated with cyclosporin A (CsA), a potent immuno-suppressant. The development of autoimmune disease in the nu/nu mice was prevented by inoculation of thymocyte suspensions prepared from normal nu/+ mice, but not by thymocyte suspensions from CsA-treated nu/+ mice. Cotransplantation of normal nu/+ mouse thymus with CsA-treated thymus also suppressed the development of autoimmune disease. Inoculation of spleen cell suspensions prepared from normal adult nu/+ mice prevented autoimmune disease, but inoculation of those from newborn nu/+ mice did not. Thus, CsA appears to interfere selectively with the thymic production of certain suppressor T cells controlling self-reactive (autoimmune) T cells, allowing the latter to expand and cause autoimmune disease.

scholarly journals Autoimmune disease as a consequence of developmental abnormality of a T cell subpopulation.

1996 ◽  
Vol 184 (2) ◽  
pp. 387-396 ◽  
Author(s):  
M Asano ◽  
M Toda ◽  
N Sakaguchi ◽  
S Sakaguchi
Keyword(s):  
T Cells ◽  
Autoimmune Diseases ◽  
Spleen Cell ◽  
Interleukin 2 ◽  
Cell Suspensions ◽  
Cell Subpopulation ◽  
Adult Mice ◽  
Self Tolerance ◽  
Organ Specific ◽  
Cytokine Formation

Neonatal thymectomy (NTx), especially around day 3 after birth, causes various organ-specific autoimmune diseases in mice. This report shows that: (a) T cells expressing the interleukin 2 receptor alpha chains (CD25) ontogenically begin to appear in the normal periphery immediately after day 3, rapidly increasing within 2 wk to nearly adult levels (approximately 10% of CD3+ cells, especially of CD4+ cells); (b) NTx on day 3 eliminates CD25+ T cells from the periphery for several days; inoculation immediately after NTx of CD25+ splenic T cells from syngeneic non-Tx adult mice prevents autoimmune development, whereas inoculation of CD25- T cells even at a larger dose does not; and furthermore, (c) similar autoimmune diseases can be produced in adult athymic nu/nu mice by inoculating either spleen cell suspensions from 3-d-old euthymic nu/+ mice or CD25+ cell-depleted spleen cell suspensions from older, even 1-yr-old, nu/+ mice. The CD25- populations from neonates or adults are also similar in the profile of cytokine formation. These results, taken together, indicate that one aspect of peripheral self-tolerance is maintained by CD25+ T cells that sustain potentially pathogenic self-reactive T cells in a CD25- dormant state; the thymic production of the former is developmentally programmed to begin on day 3 after birth in mice. Thus, NTx on day 3 can, at least transiently, eliminate/reduce the autoimmune-preventive CD25+ T cells, thereby leading to activation of the self-reactive T cells that have been produced before NTx.

scholarly journals Organ-specific autoimmune diseases induced in mice by elimination of T cell subset. I. Evidence for the active participation of T cells in natural self-tolerance; deficit of a T cell subset as a possible cause of autoimmune disease.

1985 ◽  
Vol 161 (1) ◽  
pp. 72-87 ◽  
Author(s):  
S Sakaguchi ◽  
K Fukuma ◽  
K Kuribayashi ◽  
T Masuda
Keyword(s):  
T Cells ◽  
T Cell ◽  
Autoimmune Disease ◽  
Autoimmune Diseases ◽  
Nude Mice ◽  
Cell Subset ◽  
Spleen Cells ◽  
Histological Lesion ◽  
T Cell Subset ◽  
Organ Specific

Organ-specific autoimmune diseases such as oophoritis, gastritis, thyroiditis, and orchitis were induced in female or male nude (nu/nu) mice by the transfer of nu/+spleen cells from which particular Lyt T cell subset(s) had been removed: nu/+spleen cells treated with anti-Lyt-1 plus complement (C) caused disease in recipient nude mice; anti-Lyt-2 plus C-treated spleen cells, in contrast, did not. The cells responsible for disease induction are believed to be Thy-1+, Lyt-1-, 2,3- (Thy-1, Lyt-1, 2,3), since spleen cells treated with mixed antisera, including anti-Lyt-1 and anti-Lyt-2, plus C, could induce the disease with almost the same incidence as anti-Lyt-1 plus C-treated cells (oophoritis 50%, gastritis 25%, thyroiditis 10-20%, and orchitis 40%). Cells treated with mixed antisera of anti-Thy-1, anti-Lyt-1, and anti-Lyt-2, plus C, could not induce autoimmune disease. Each induced autoimmune disease could be adoptively transferred to other nude mice via spleen cells, with resulting histological lesion of corresponding organs and development of specific circulating autoantibodies. Since anti-Thy-1 plus C treatment of donor spleen cells abrogated the capacity to transfer the disease, we conclude that T cells are required as effector cells, and that these may develop from Lyt-1-, 2,3- cells. Lyt-1+, 2,3- cells were demonstrated to have suppressive activity upon the development of the diseases; induction of autoimmunity was completely inhibited by the cotransfer of Lyt-1+, 2,3- cells with Lyt-1-, 2,3- cells. When anti-Lyt-2 plus C-treated cells (i.e., Lyt-1+, 2,3- and Lyt-1-, 2,3- cells) were mixed with anti-Lyt-1 and anti-Lyt-2 plus C-treated cells (i.e., Lyt-1-, 2,3- cells) in various ratios, then transferred to nude mice, the development of each autoimmune disease was clearly inhibited, even by small doses of Lyt-1+, 2,3- cells. The autoimmune disease we were able to induce was quite similar to human organ-specific autoimmune disease in terms of the spectrum of organs involved, histopathological features, and the development of autoantibodies to corresponding organ components (oocytes, parietal cells, thyroid colloid, including thyroglobulin, and sperm).(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Thymus and autoimmunity: capacity of the normal thymus to produce pathogenic self-reactive T cells and conditions required for their induction of autoimmune disease.

1990 ◽  
Vol 172 (2) ◽  
pp. 537-545 ◽  
Author(s):  
S Sakaguchi ◽  
N Sakaguchi
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Bone Marrow Transplantation ◽  
T Cell ◽  
Autoimmune Disease ◽  
Autoimmune Diseases ◽  
Rheumatoid Factors ◽  
Systemic Autoimmune Diseases ◽  
Organ Specific ◽  
Gastric Parietal Cells

BALB/c athymic nu/nu mice spontaneously developed organ-specific (gastritis, thyroiditis, oophoritis, or orchitis) and systemic (arteritis, glomerulonephritis, and polyarthritis) autoimmune diseases when transplanted with neonatal BALB/c thymuses. Transplantation of thymuses from adult BALB/c mice was far less effective in inducing histologically evident organ-specific autoimmune disease in nu/nu mice. Autoimmune disease developed, however, when adult thymuses were irradiated at a T cell-depleting dose before transplantation. Engrafting newborn thymuses into BALB/c mice T cell depleted by thymectomy, irradiation, and bone marrow transplantation produced similar organ-specific autoimmune disease as well, but thymus engrafting into T cell-nondepleted BALB/c mice (i.e., mice thymectomized as adults, but not irradiated) did not, despite the fact that transplanted thymuses grew well in both groups of mice. The mice with organ-specific autoimmune disease produced autoantibodies specific for the respective organ components, such as gastric parietal cells, thyroglobulins, oocytes, or sperm. The thymus-transplanted nu/nu mice also had hypergammaglobulinemia and developed anti-DNA autoantibodies, rheumatoid factors, and immune complexes in the circulation. These results indicate that: (a) the thymus of a murine strain that does not develop spontaneous autoimmune disease can produce pathogenic self-reactive T cells that mediate organ-specific and/or systemic autoimmune diseases; and (b) such self-reactive T cells, especially those mediating organ-specific autoimmune disease, spontaneously expand and cause autoimmune disease when released to the T cell-deficient or -eliminated periphery.

scholarly journals Defective Suppressor Function of Human CD4+ CD25+ Regulatory T Cells in Autoimmune Polyglandular Syndrome Type II

2004 ◽  
Vol 199 (9) ◽  
pp. 1285-1291 ◽  
Author(s):  
Martin A. Kriegel ◽  
Tobias Lohmann ◽  
Christoph Gabler ◽  
Norbert Blank ◽  
Joachim R. Kalden ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Autoimmune Diseases ◽  
Type I ◽  
Type Ii ◽  
Central Tolerance ◽  
Autoimmune Polyglandular Syndrome ◽  
Healthy Donors ◽  
Organ Specific ◽  
Autoimmune Polyglandular Syndrome Type

In autoimmune polyglandular syndromes (APS), several organ-specific autoimmune diseases are clustered. Although APS type I is caused by loss of central tolerance, the etiology of APS type II (APS-II) is currently unknown. However, in several murine models, depletion of CD4+ CD25+ regulatory T cells (Tregs) causes a syndrome resembling human APS-II with multiple endocrinopathies. Therefore, we hypothesized that loss of active suppression in the periphery could be a hallmark of this syndrome. Tregs from peripheral blood of APS-II, control patients with single autoimmune endocrinopathies, and normal healthy donors showed no differences in quantity (except for patients with isolated autoimmune diseases), in functionally important surface markers, or in apoptosis induced by growth factor withdrawal. Strikingly, APS-II Tregs were defective in their suppressive capacity. The defect was persistent and not due to responder cell resistance. These data provide novel insights into the pathogenesis of APS-II and possibly human autoimmunity in general.

Th1 and Th2 CD4+ T cells in the pathogenesis of organ-specific autoimmune diseases

1995 ◽  
Vol 16 (1) ◽  
pp. 34-38 ◽  
Author(s):  
Roland S. Liblau ◽  
Steven M. Singer ◽  
Hugh O. McDevitt
Keyword(s):  
T Cells ◽  
Autoimmune Diseases ◽  
Cd4 T Cells ◽  
Organ Specific ◽  
Th1 And Th2

scholarly journals Autoimmune thyroid disease and other non-endocrine autoimmune diseases

2011 ◽  
Vol 64 (3-4) ◽  
pp. 183-187 ◽  
Author(s):  
Ljiljana Todorovic-Djilas ◽  
Tijana Icin ◽  
Jovanka Novakovic-Paro ◽  
Ivana Bajkin
Keyword(s):  
Autoimmune Disease ◽  
Autoimmune Diseases ◽  
Lupus Erythematosus ◽  
Thyroid Disease ◽  
Autoimmune Thyroid Disease ◽  
Good Reason ◽  
The Body ◽  
Autoimmune Thyroid Diseases ◽  
Autoimmune Thyroid ◽  
Organ Specific

Introduction, Autoimmune diseases are chronic conditions initiated by the loss of immunological tolerance to self-antigens. They constitute heterogeneous group of disorders, in which multiple alterations in the immune system result in a spectrum of syndromes that either target specific organs or affect the body systematically. Recent epidemiological studies have shown a possible shift of one autoimmune disease to another or the fact that more than one autoimmune disease may coexist in a single patient or in the same family. Numerous autoimmune diseases have been shown to coexist frequently with thyroid autoimmune diseases. Autoimmune thyroid disease and other organ specific non-endocrine autoimmune diseases. This part of the study reviews the prevalence of autoimmune thyroid disease coexisting with: pernicious anaemia, vitiligo, celiac disease, autoimmune liver disease, miastenia gravis, alopecia areata and sclerosis multiplex, and several recommendations for screening have been given. Autoimmune thyroid disease and other organ non-specific non-endocrine autoimmune diseases. Special attention is given to the correlation between autoimmune thyroid disease and rheumatoid arthritis, systemic lupus erythematosus, syndrome Sj?gren, systemic sclerosis and mixed connective tissue disease. Conclusions. Screening for autoimmune thyroid diseases should be recommended in everyday clinical practice, in patients with primary organ-specific or organ non-specific autoimmune disease. Other?wise, in patients with primary thyroid autoimmune disease, there is no good reason of seeking for all other autoimmune diseases, although these patients have a greater risk of developing other autoimmune disease. Economic aspects of medicine require further analyzing of these data, from cost/benefit point of view to justified either mandatory screening or medical practitioner judgment.

scholarly journals CD4+CD25+ T Cells Prevent the Development of Organ-Specific Autoimmune Disease by Inhibiting the Differentiation of Autoreactive Effector T Cells

2005 ◽  
Vol 175 (11) ◽  
pp. 7135-7142 ◽  
Author(s):  
Richard J. DiPaolo ◽  
Deborah D. Glass ◽  
Karen E. Bijwaard ◽  
Ethan M. Shevach
Keyword(s):  
T Cells ◽  
Autoimmune Disease ◽  
Effector T Cells ◽  
Organ Specific

scholarly journals STAT3 deficiency in B cells exacerbates uveitis by promoting expansion of pathogenic lymphocytes and suppressing regulatory B cells (Bregs) and Tregs

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Favour O. Oladipupo ◽  
Cheng-Rong Yu ◽  
Ezekiel Olumuyide ◽  
Yingyos Jittaysothorn ◽  
Jin Kyeong Choi ◽  
...  
Keyword(s):  
T Cells ◽  
B Cells ◽  
Autoimmune Diseases ◽  
B Lymphocyte ◽  
Kinase Inhibitors ◽  
Autoimmune Encephalitis ◽  
Cyclin Dependent Kinase ◽  
Organ Specific ◽  
Enhanced Expression ◽  
Experimental Autoimmune

Abstract STAT3 transcription factor induces differentiation of naïve T cells into Th17 cells and loss of STAT3 in T cell prevents development of CNS autoimmune diseases. However, function of STAT3 in the B lymphocyte subset is not well understood. In this study, we have generated mice lacking STAT3 in CD19+ B cells (CD19-STAT3KO) and investigated intrinsic and extrinsic functions of STAT3 in B cells and its potential role in resistance or pathogenesis of organ-specific autoimmune diseases. We show that STAT3 regulates metabolic mechanisms in B cells with implications for bioenergetic and metabolic pathways that control cellular homeostasis in B cells. Thus, loss of STAT3 in CD19-STAT3KO cells perturbed growth and apoptosis by inducing rapid entry of B cells into the S-phase of the cell cycle, decreasing expression of cyclin-dependent kinase inhibitors and upregulating pro-apoptotic proteins. We further show that the CD19-STAT3KO mice develop severe experimental autoimmune uveitis (EAU), an animal model of human uveitis. Exacerbated uveitis in CD19-STAT3KO mice derived in part from enhanced expression of costimulatory molecules on B cells, marked increase of Th17 responses and increased recruitment of granulocytes into the neuroretina. The enhanced autoimmunity upon deletion of STAT3 in B cells is also recapitulated in experimental autoimmune encephalitis, a mouse model of multiple sclerosis and thus support our conclusion that STAT3 deletion in B cells enhanced inflammation and the effects observed are not model specific. Our data further indicate that STAT3 pathway modulates interactions between B and T cells during EAU resulting in alteration of lymphocyte repertoire by increasing levels of autoreactive pathogenic T cells while suppressing development and/or expansion of immune-suppressive lymphocytes (Bregs and Tregs). Taken together, STAT3 exerts diametrically opposite effects in lymphocytes, with loss of STAT3 in B cells exacerbating uveitis whereas Stat3 deletion in T cells confers protection.

Innate Immunity in Idiopathic Thrombocytopenic Purpura (ITP)

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4907-4907
Author(s):  
Akio Saito ◽  
Akihiko Yokohama ◽  
Hirotaka Nakahashi ◽  
Kohtaro Toyama ◽  
Takeki Mitsui ◽  
...  
Keyword(s):  
Innate Immunity ◽  
T Cells ◽  
Autoimmune Disease ◽  
Autoimmune Diseases ◽  
Nk Cells ◽  
Th17 Cells ◽  
Inkt Cells ◽  
Thrombocytopenic Purpura ◽  
Hla Dr ◽  
H Pylori

Abstract Background: Dendritic cells (DCs), natural killer (NK) cells, and invariant NKT (iNKT) cells play important roles in innate immune systems. These cells have recently been shown to be involved in immunoregulation, and some studies have suggested associations with various kinds of autoimmune disease. Conversely, regulatory T cells (Tregs) that are important for peripheral tolerance and Th17 cells that play a central role in maintenance of chronic inflammation are also associated with the pathogenesis of several autoimmune diseases. Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disease mediated by anti-platelet autoantibodies, but relationships to innate immunity are unclear. In addition, the pathogenesis of ITP associated with Helicobacter pylori remains obscure. In particular, the regulation of immune responses by these cells in patients infected with H. pylori has not been investigated. This study analyzed DCs, NK cells, iNKT cells, Tregs and Th17 cells in patients with ITP. Methods: Subjects comprised 31 patients with ITP and 22 healthy donors. Study protocols were approved by the Institutional Review Board of Gunma University Hospital, and written informed consent was obtained from all subjects. Flow cytometry was used to investigate amounts of circulating plasmacytoid DCs (pDCs) (CD123+ HLA−DR+) and myeloid DCs (mDCs) (CD11c+ HLA−DR+) from whole white blood cells, and NK cells (CD3− CD56+), iNKT cells (Vα24+ Vβ11+), Tregs (CD4+ CD25+ Foxp3+) and Th17 cells (CD4+ IL−17A+) from mononuclear cells. The intracellular interleukin (IL)-17A production in CD4+ T-cells activated by phorbol 12-myristate 13-acetate (PMA) and ionomycin was assessed to detect Th17 cells. Results: Both the percentage and numbers of pDCs were significantly reduced in patients compared to healthy controls (p<0.001), while those of mDCs tended to be lower in patients than in controls, but with no significant differences. NK cell counts tended to be higher in patients than in controls and counts of iNKT cells tended to be lower in patients than in controls, but again no significant differences were demonstrated. Notably, Treg levels were comparable between patients and controls, while Th17 cells were significantly increased in patients compared with controls (p<0.002). In all cases, no significant differences were demonstrated between patients with H. pylori-positive and -negative results. Conclusion: These results suggest that alterations in innate immunity as a reduction of pDCs could be associated with the pathogenesis of ITP. Furthermore, as in some autoimmune diseases that have been considered as Th1 diseases, Th17 cells may play an important role in ITP.

Clonal anergy in self-reactive α/β T cells is abrogated by heat-shock protein-reactive γ/δ T cells in aged athymic nude mice

1990 ◽  
Vol 20 (7) ◽  
pp. 1475-1482 ◽  
Author(s):  
Hiroyuki Yuuki ◽  
Yasunobu Yoshikai ◽  
Kenji Kishihara ◽  
Akinori Iwasaki ◽  
Goto Matsuzaki ◽  
...  
Keyword(s):  
T Cells ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Nude Mice ◽  
Athymic Nude Mice ◽  
Clonal Anergy
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