Predominant intraepithelial localization of primed T cells and immunoglobulin-producing lymphocytes in Graves' disease

1991 ◽  
Vol 124 (6) ◽  
pp. 630-636 ◽  
Author(s):  
R. Paschke ◽  
N. Brückner ◽  
R. Schmeidl ◽  
P. Pfiester ◽  
K. H. Usadel
Keyword(s):  
T Cells ◽  
T Lymphocytes ◽  
Lymphocytic Infiltration ◽  
Intraepithelial Lymphocytes ◽  
Pokeweed Mitogen ◽  
Graves Disease ◽  
Immunoglobulin Synthesis ◽  
Thyroid Glands ◽  
Staining Index

Abstract. It has been proposed that intrathyroidal lymphocytes, localized in specific anatomical sites might have distinct, pathophysiologically relevant functions in Graves' disease. However, most studies of intrathyroidal lymphocytes were restricted to two lymphocyte locations and used semiquantitative methods. Therefore we used seven anatomically different lymphoid compartments to classify and evaluate by quantitative representative methods the total intrathyroidal lymphocytic infiltration and the staining indexes for immunoglobulin-producing plasmocytes and primed T cells (CD45RO), which provide maximum help to pokeweed mitogen-stimulated immunoglobulin synthesis in 36 thyroid glands from patients with Graves' disease. We found only 3.4% of all intrathyroidal lymphocytes intraepithelially. However, only intraepithelial lymphocytes showed a significantly higher staining index for primed T cells compared with several other compartments. There was also a high staining index for immunoglobulin-producing lymphocytes in this compartment. Kappa- and lambda-positive plasmocytes were found in a polyclonal distribution (kappa:lambda=64.1: 35.9) in all compartments. This increased incidence of CD45RO-positive T lymphocytes and of immunoglobulin-producing lymphocytes among the intraepithelial lymphocytes suggests a distinct pathophysiological function of lymphocytes in peripolesis in Graves' disease. Furthermore, there is a polyclonal intrathyroidal immunoglobulin synthesis.

scholarly journals In vitro regulation of immunoglobulin synthesis after human marrow transplantation. II. Deficient T and non-T lymphocyte function within 3- 4 months of allogeneic, syngeneic, or autologous marrow grafting for hematologic malignancy

Blood ◽  
1982 ◽  
Vol 59 (4) ◽  
pp. 844-850 ◽  
Author(s):  
RP Witherspoon ◽  
LG Lum ◽  
R Storb ◽  
ED Thomas
Keyword(s):  
T Cells ◽  
T Lymphocytes ◽  
Mononuclear Cells ◽  
Hematologic Malignancy ◽  
Plaque Assay ◽  
Pokeweed Mitogen ◽  
Lymphocyte Function ◽  
Peripheral Blood Mononuclear ◽  
Immunoglobulin Secretion

Abstract Immunoglobulin secretion was studied in 37 patients between 19 and 106 days after allogeneic HLA-identical (30 patients), allogeneic one HLA- haplotype-identical (three patients), syngeneic (three patients), or autologous (one patient) marrow grafting. E rosette-positive (T) and E rosette-negative (non-T) peripheral blood mononuclear cells were cocultured with pokeweed mitogen for 6 days. Polyvalent immunoglobulin secretion was determined by counting plaque forming cells in a reverse hemolytic plaque assay. The number of antibody secreting cells in cocultures of autologous T and non-T lymphocytes was low in 40 of 44 tests conducted on samples from the 37 patients. Mononuclear or non-T cells from 38 of 40 tests failed to produce antibody when cultured with normal helper T cells. T cells from 23 of 37 tests failed to help normal non-T cells secrete antibody. T lymphocytes from 23 of 41 tests suppressed antibody production greater than 80% by normal T and non-T cells. The suppressor cells were radiosensitive in 17 of the 25 tests. The abnormal function of lymphocyte subpopulations in patients during the first 3 mo after syngeneic, allogeneic or autologous marrow grafting was similar regardless of the type of graft or the presence of acute graft versus host disease.

scholarly journals Induction of in vitro differentiation and immunoglobulin synthesis of human leukemic B lymphocytes.

1978 ◽  
Vol 148 (6) ◽  
pp. 1570-1578 ◽  
Author(s):  
S M Fu ◽  
N Chiorazzi ◽  
H G Kunkel ◽  
J P Halper ◽  
S R Harris
Keyword(s):  
T Cells ◽  
B Cells ◽  
Plasma Cells ◽  
Lymphocytic Leukemia ◽  
Leukemic Cells ◽  
Pokeweed Mitogen ◽  
In Vitro Differentiation ◽  
Immunoglobulin Synthesis

Successful induction of in vitro differentiation and immunoglobulin synthesis of the leukemic lymphocytes was carried out in two cases of chronic lymphocytic leukemia. Few plasma cells and little specific Ig secretion were detected in the cultures of isolated leukemic B cells in either the presence or the absence of autologous T cells. Up to 30% of the leukemic B cells matured to plasma cells, and a 32-fold increase in specific Ig synthesis was observed when T cells from normal individuals were added to the cultures of these leukemic B cells. In one of the two cases, autologous T cells were able to induce greater than 50% of the leukemic B cells to differentiate further to plasma cells in the presence of pokeweed mitogen. This markedly accelerated in vitro differentiation was only achieved with leukemic cells from cases in which there was evidence of slight differentiation in vivo. No evidence could be obtained for excessive suppressor T cells in these patients. However, a T-cell defect in the generation of allogeneic effect helper factors was identified. This defect may be responsible for the reduced rate of leukemic maturation in vivo.

scholarly journals Expression of adhesion molecules on infiltrating T cells in thyroid glands from patients with Graves' disease

2008 ◽  
Vol 94 (2) ◽  
pp. 363-370 ◽  
Author(s):  
N. ISHIKAWA ◽  
K. EGUCHI ◽  
Y. UEKI ◽  
M. NAKASHIMA ◽  
H. SHIMADA ◽  
...  
Keyword(s):  
T Cells ◽  
Adhesion Molecules ◽  
Graves Disease ◽  
Thyroid Glands

In vitro cellular interactions among thyrocytes, T cells and monocytes from patients with Graves' disease

1988 ◽  
Vol 117 (2) ◽  
pp. 282-288 ◽  
Author(s):  
Toshio Otsubo ◽  
Katsumi Eguchi ◽  
Chikako Shimomura ◽  
Yukitaka Ueki ◽  
Hiroshi Tezuka ◽  
...  
Keyword(s):  
T Cells ◽  
Antigen Expression ◽  
Interferon Γ ◽  
Graves Disease ◽  
Cellular Interactions ◽  
Activated T Cells ◽  
Hla Dr ◽  
Thyroid Glands ◽  
Culture Supernatants

Abstract. In order to investigate the cellular interactions among thyrocytes, T cells and monocytes in thyroid glands from patients with Graves' disease, we determined alterations of HLA-DR antigen expression on thyrocytes and T cells, and the production of interferon-γ during coculture of thyrocytes, T cells and monocytes obtained from patients with Graves' disease. Thyroid glands were obtained at operation from 17 patients with Graves' disease. When thyrocytes and autologous peripheral blood T cells were cocultured for 7 days, the percentage of HLA-DR antigen expression on thyroyctes was significantly increased by T cells and that on T cells was also significantly increased by thyrocytes. Addition of autologous monocytes to the mixtures of thyrocytes and T cells significantly increased the expression of HLA-DR antigens on both thyrocytes and T cells compared with mixtures without monocytes. In culture supernatants, inteferon-γ was detected in 4 of 14 cocultures of thyrocytes and T cells, in 5 of 10 cocultures of thyrocytes, T cells and monocytes, but not in any cultures of thyrocytes alone, T cells alone and T cells and monocytes. Induction of HLA-DR antigen expression on thyrocytes and T cells was blocked by addition of anti-interferon-γ monoclonal antibody to the mixture. These results suggest that HLA-DR antigen positive thyrocytes are able to induce the HLA-DR antigen expression of T cells in the presence of monocytes, and the activated T cells are capable of producing interferon-γ which acts on thyrocytes to induce and maintain the expression of HLA-DR antigens.

Dysfunction of Suppressor T Cells in Thyroid Glands from Patients with Graves' Disease

1987 ◽  
Vol 65 (5) ◽  
pp. 922-928 ◽  
Author(s):  
YUKITAKA UEKI ◽  
KATSUMI EGUCHI ◽  
TAKAAKI FUKUDA ◽  
TOSHIO OTSUBO ◽  
YOJIRO KAWABE ◽  
...  
Keyword(s):  
T Cells ◽  
Graves Disease ◽  
Suppressor T Cells ◽  
Thyroid Glands

scholarly journals In vitro regulation of immunoglobulin synthesis after human marrow transplantation. II. Deficient T and non-T lymphocyte function within 3- 4 months of allogeneic, syngeneic, or autologous marrow grafting for hematologic malignancy

Blood ◽  
1982 ◽  
Vol 59 (4) ◽  
pp. 844-850 ◽  
Author(s):  
RP Witherspoon ◽  
LG Lum ◽  
R Storb ◽  
ED Thomas
Keyword(s):  
T Cells ◽  
T Lymphocytes ◽  
Mononuclear Cells ◽  
Hematologic Malignancy ◽  
Plaque Assay ◽  
Pokeweed Mitogen ◽  
Lymphocyte Function ◽  
Peripheral Blood Mononuclear ◽  
Immunoglobulin Secretion

Immunoglobulin secretion was studied in 37 patients between 19 and 106 days after allogeneic HLA-identical (30 patients), allogeneic one HLA- haplotype-identical (three patients), syngeneic (three patients), or autologous (one patient) marrow grafting. E rosette-positive (T) and E rosette-negative (non-T) peripheral blood mononuclear cells were cocultured with pokeweed mitogen for 6 days. Polyvalent immunoglobulin secretion was determined by counting plaque forming cells in a reverse hemolytic plaque assay. The number of antibody secreting cells in cocultures of autologous T and non-T lymphocytes was low in 40 of 44 tests conducted on samples from the 37 patients. Mononuclear or non-T cells from 38 of 40 tests failed to produce antibody when cultured with normal helper T cells. T cells from 23 of 37 tests failed to help normal non-T cells secrete antibody. T lymphocytes from 23 of 41 tests suppressed antibody production greater than 80% by normal T and non-T cells. The suppressor cells were radiosensitive in 17 of the 25 tests. The abnormal function of lymphocyte subpopulations in patients during the first 3 mo after syngeneic, allogeneic or autologous marrow grafting was similar regardless of the type of graft or the presence of acute graft versus host disease.

scholarly journals The mouse gut T lymphocyte, a novel type of T cell. Nature, origin, and traffic in mice in normal and graft-versus-host conditions.

1978 ◽  
Vol 148 (6) ◽  
pp. 1661-1677 ◽  
Author(s):  
D Guy-Grand ◽  
C Griscelli ◽  
P Vassalli
Keyword(s):  
T Cells ◽  
Mast Cells ◽  
T Lymphocytes ◽  
Intestinal Mucosa ◽  
Cell Types ◽  
Intraepithelial Lymphocytes ◽  
Graft Versus Host ◽  
Dividing Cells ◽  
Gut Mucosa ◽  
Chediak Higashi Syndrome

Lymphocytes of the mouse intestinal mucosa, identified in tissue sections or purified suspensions of intraepithelial lymphocytes as T cells (gut T lymphocytes [GTL]), were studied in normal mice or in beige mice (the equivalent of the Chediak-Higashi syndrome in man, characterized by giant granules in various cell types, including mast cells). Mice were studied in normal or in germ-free conditions, or during a graft versus host (GVH) reaction resulting from the injection of parental thymocytes into lethally irradiated F1 mice, a condition leading to massive accumulation of T lymphocytes of donor origin in the host gut mucosa. In normal as well as in GVH conditions, a high percentage of the gut IE lymphocytes contain granules (up to 80% in the beige mouse). These granules have ultrastructural, hostochemical and other features resembling those of mast cell granules; in beige mice, up to 50% of them can be shown to contain histamine. Granulated T cells are also found in the lamina propria. It appears that the GTL may progressively lose their surface T antigens when the granules become more developed. Kinetics of [3H]TdR labeling of the GTL, transfer experiments with T cells of various origins, selective [3H]TdR labeling and selective irradiation of the Peyer's patches (PP), and effect of thoraic duct (TD) drainage led to the conclusion that GTL are the progeny of T cells stimulated to divide in the PP microenvironment, which endows them with a gut-homing tendency. From the PP, these cells follow a cycle, migrating to the TD and to the blood to colonize the whole intestinal mucosa, the majority of them as dividing cells undergoing a single round of traffic, with some probably able to recirculate and becoming a more long-lived variety. Antigenic stimulation within the PP is necessary for the emergence of GTL progenitors, but their gut-homing property is unrelated to the antigen as shown with fetal gut grafts, notably in GVH where grafts syngeneic to the host or donor become similarly infiltrated by GTL. On the basis of their properties and of further evidence to be reported elsewhere, it is proposed that GTL belong to a special class of T lymphocytes, related to the immune defenses of the mucosal systems in general, and capable of acting as progenitors of mucosal mast cells.

scholarly journals The Link between Graves’ Disease and Hashimoto’s Thyroiditis: A Role for Regulatory T Cells

Endocrinology ◽  
2007 ◽  
Vol 148 (12) ◽  
pp. 5724-5733 ◽  
Author(s):  
Sandra M. McLachlan ◽  
Yuji Nagayama ◽  
Pavel N. Pichurin ◽  
Yumiko Mizutori ◽  
Chun-Rong Chen ◽  
...  
Keyword(s):  
T Cells ◽  
Antibody Response ◽  
Hashimoto’S Thyroiditis ◽  
Lymphocytic Infiltration ◽  
Hashimoto's Thyroiditis ◽  
Thyroid Peroxidase ◽  
Graves Disease ◽  
Wild Type ◽  
Treg Depletion ◽  
A Subunit

Hyperthyroidism in Graves’ disease is caused by thyroid-stimulating autoantibodies to the TSH receptor (TSHR), whereas hypothyroidism in Hashimoto’s thyroiditis is associated with thyroid peroxidase and thyroglobulin autoantibodies. In some Graves’ patients, thyroiditis becomes sufficiently extensive to cure the hyperthyroidism with resultant hypothyroidism. Factors determining the balance between these two diseases, the commonest organ-specific autoimmune diseases affecting humans, are unknown. Serendipitous findings in transgenic BALB/c mice, with the human TSHR A-subunit targeted to the thyroid, shed light on this relationship. Of three transgenic lines, two expressed high levels and one expressed low intrathyroidal A-subunit levels (Hi- and Lo-transgenics, respectively). Transgenics and wild-type littermates were depleted of T regulatory cells (Treg) using antibodies to CD25 (CD4+ T cells) or CD122 (CD8+ T cells) before TSHR-adenovirus immunization. Regardless of Treg depletion, high-expressor transgenics remained tolerant to A-subunit-adenovirus immunization (no TSHR antibodies and no hyperthyroidism). Tolerance was broken in low-transgenics, although TSHR antibody levels were lower than in wild-type littermates and no mice became hyperthyroid. Treg depletion before immunization did not significantly alter the TSHR antibody response. However, Treg depletion (particularly CD25) induced thyroid lymphocytic infiltrates in Lo-transgenics with transient or permanent hypothyroidism (low T4, elevated TSH). Neither thyroid lymphocytic infiltration nor hypothyroidism developed in similarly treated wild-type littermates. Remarkably, lymphocytic infiltration was associated with intermolecular spreading of the TSHR antibody response to other self thyroid antigens, murine thyroid peroxidase and thyroglobulin. These data suggest a role for Treg in the natural progression of hyperthyroid Graves’ disease to Hashimoto’s thyroiditis and hypothyroidism in humans.

Regional stimulation of thyroid epithelial cells in Graves' disease by lymphocytic aggregates and plasma cells

1991 ◽  
Vol 125 (4) ◽  
pp. 459-465 ◽  
Author(s):  
Ralf Paschke ◽  
Norbert Brückner ◽  
Thomas Eck ◽  
Ludwig Schaaf ◽  
Walter Back ◽  
...  
Keyword(s):  
T Cells ◽  
Plasma Cells ◽  
Memory T Cells ◽  
Nuclear Volume ◽  
Graves Disease ◽  
Thyroid Epithelial Cell ◽  
Thyroid Glands ◽  
Functional Stimulation ◽  
Stimulation Of

Abstract. The significance of intrathyroidal lymphocytic infiltration is not known. However, several indirect lines of evidence suggest that interstitial or intraepithelial lymphocytes are the effector or thyroid autoantibodyproducing lymphocytes in Graves' disease. This has not been investigated in vivo. Changes of nuclear volume of endocrine cells have previously been shown to be a reliable parameter of functional stimulation of endocrine glands. Therefore we investigated this parameter near and off lymphocytic aggregates, loosely distributed plasma cells and memory T cells in paraffine sections of Graves' disease thyroid glands. In 21 Graves' disease thyroid glands we found significant increases of thyroid epithelial cell nuclear volume near plasma cells (198.4 μm3) as well as near lymphocytic aggregates (219.1 μm3) compared with thyroid epithelial cell nuclear volume one microscopic field away (160.1 and 137.7 μm3 respectively). Similar nuclear volume differences were observed after propanolol and thiourelene antithyroid drug treatment. These nuclear volume differences could not be observed in 10 control thyroid glands and around CD45R0-positive memory T cells in Graves' disease thyroid glands. These direct in vivo investigations of regional functional stimulation of thyroid epithelial cells in Graves' disease show local stimulation near lymphocytic aggregates and diffusely distributed plasma cells. Therefore our in vivo data do not permit to identify stimulatory lymphocytes only interstitially or intraepithelially as previously suggested.

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