scholarly journals A type 2 cytokine axis for thymus emigration

2017 ◽  
Vol 214 (8) ◽  
pp. 2205-2216 ◽  
Author(s):  
Andrea J. White ◽  
Song Baik ◽  
Sonia M. Parnell ◽  
Amanda M. Holland ◽  
Frank Brombacher ◽  
...  
Keyword(s):  
T Cells ◽  
Stromal Cells ◽  
Perivascular Spaces ◽  
Thymocyte Development ◽  
Invariant Nkt Cells ◽  
Developmental Program ◽  
Innate T Cells ◽  
Type 2 Cytokines ◽  
Thymic Stromal Cells

In the thymus, stromal microenvironments support a developmental program that generates mature T cells ready for thymic exit. The cellular and molecular specialization within thymic stromal cells that enables their regulation of specific stages of thymocyte development is poorly understood. Here, we show the thymic microenvironment expresses the type 2 IL-4R complex and is functionally responsive to its known ligands, IL-4 and IL-13. Absence of IL-4Rα limits thymocyte emigration, leading to an intrathymic accumulation of mature thymocytes within medullary perivascular spaces and reduced numbers of recent thymic emigrants. Thymus transplantation shows this requirement maps to IL-4Rα expression by stromal cells, and we provide evidence that it regulates thymic exit via a process distinct from S1P-mediated migration. Finally, we reveal a cellular mechanism by which IL-4+IL-13+ invariant NKT cells are necessary for IL-4Rα signaling that regulates thymic exit. Collectively, we define a new axis for thymic emigration involving stimulation of the thymic microenvironment via type 2 cytokines from innate T cells.

T cells specific for Candida albicans antigens and producing type 2 cytokines in lesional mucosa of untreated HIV-infected patients with pseudomembranous oropharyngeal candidiasis

2008 ◽  
Vol 10 (2) ◽  
pp. 166-174 ◽  
Author(s):  
Alessandra Vultaggio ◽  
Letizia Lombardelli ◽  
Maria Grazia Giudizi ◽  
Roberta Biagiotti ◽  
Benedetta Mazzinghi ◽  
...  
Keyword(s):  
T Cells ◽  
Candida Albicans ◽  
Oropharyngeal Candidiasis ◽  
Type 2 Cytokines

Peyer's patch CD8+ memory T cells secrete T helper type 1 and type 2 cytokines and provide help for immunoglobulin secretion

1994 ◽  
Vol 24 (12) ◽  
pp. 3087-3092 ◽  
Author(s):  
Anand S. Lagoo ◽  
John H. Eldridge ◽  
Sandhya Lagoo-Deenadaylan ◽  
C. Allen Black ◽  
Ben U. Ridwan ◽  
...  
Keyword(s):  
T Cells ◽  
Memory T Cells ◽  
T Helper ◽  
Peyer's Patch ◽  
Immunoglobulin Secretion ◽  
Type 2 Cytokines ◽  
Cd8 Memory T Cells ◽  
Helper Type

scholarly journals Dysregulated Synthesis of Intracellular Type 1 and Type 2 Cytokines by T Cells of Patients with Cutaneous T-Cell Lymphoma

1999 ◽  
Vol 6 (1) ◽  
pp. 79-84 ◽  
Author(s):  
Bang-Ning Lee ◽  
Madeleine Duvic ◽  
Chih-Kwang Tang ◽  
Carlos Bueso-Ramos ◽  
Zeev Estrov ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Lymphoma ◽  
Study Groups ◽  
Cutaneous T Cell Lymphoma ◽  
Healthy Donors ◽  
Type 2 Cytokines ◽  
Ifn Γ

ABSTRACT Mycosis fungoides (MF) and Sezary syndrome (SS) are the two main clinical entities of cutaneous T-cell lymphoma (CTCL). As the disease progresses from MF to SS, a switch from a type 1 (interleukin [IL]-2 and gamma interferon [IFN-γ]) to a type 2 (IL-4) cytokine production profile occurs. Although roles for type 1 and type 2 cytokines in the pathogenesis of CTCL have been proposed, the cellular origins of these cytokines are unclear. Using flow cytometry to identify individual T-cell subsets, we studied cytokine synthesis by the T cells of 13 patients with SS and 12 with MF and 9 hematologically healthy donors. Upon activation with phorbol 12-myristate 13-acetate (PMA), the numbers of T cells synthesizing IL-2 were similar for all study groups. Whereas the predominant T-cell producing IL-2 in healthy donors and in those with MF was CD7+, in patients with SS, it was CD7−. Although the number of IL-4+CD4+ T cells was low for all study groups, there was a significantly higher number of IL-4+ CD8+ T cells in patients with MF than in those with SS or healthy donors. There was a decline in the number of IFN-γ-producing T cells in CTCL donors compared to that in healthy donors. More importantly, there was a significant decrease in the number of IFN-γ-producing T cells with disease progression from MF to SS. The inability of these T cells to synthesize IFN-γ may have prognostic value in CTCL, since it may be responsible for the progression of the disease from MF to SS.

scholarly journals Exosomes derived from statin-modified bone marrow dendritic cells increase thymus-derived natural regulatory T cells in experimental autoimmune myasthenia gravis

2019 ◽  
Vol 16 (1) ◽  
Author(s):  
Peng Zhang ◽  
Ru-Tao Liu ◽  
Tong Du ◽  
Chun-Lin Yang ◽  
Yu-Dong Liu ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Myasthenia Gravis ◽  
Stromal Cells ◽  
Experimental Autoimmune Myasthenia Gravis ◽  
Autoimmune Myasthenia ◽  
Thymic Stromal Cells ◽  
Experimental Autoimmune

Abstract Background The thymus plays an essential role in the pathogenesis of myasthenia gravis (MG). In patients with MG, natural regulatory T cells (nTreg), a subpopulation of T cells that maintain tolerance to self-antigens, are severely impaired in the thymuses. In our previous study, upregulated nTreg cells were observed in the thymuses of rats in experimental autoimmune myasthenia gravis after treatment with exosomes derived from statin-modified dendritic cells (statin-Dex). Methods We evaluated the effects of exosomes on surface co-stimulation markers and Aire expression of different kinds of thymic stromal cells, including cTEC, mTEC, and tDCs, in EAMG rats. The isolated exosomes were examined by western blot and DLS. Immunofluorescence was used to track the exosomes in the thymus. Flow cytometry and western blot were used to analyze the expression of co-stimulatory molecules and Aire in vivo and in vitro. Results We confirmed the effects of statin-Dex in inducing Foxp3+ nTreg cells and found that both statin-Dex and DMSO-Dex could upregulate CD40 but only statin-Dex increased Aire expression in thymic stromal cells in vivo. Furthermore, we found that the role of statin-Dex and DMSO-Dex in the induction of Foxp3+ nTreg cells was dependent on epithelial cells in vitro. Conclusions We demonstrated that statin-Dex increased expression of Aire in the thymus, which may further promote the Foxp3 expression in the thymus. These findings may provide a new strategy for the treatment of myasthenia gravis.

scholarly journals Correction: Human CD141+ Dendritic Cells Induce CD4+ T Cells To Produce Type 2 Cytokines

2014 ◽  
Vol 193 (12) ◽  
pp. 6210-6210 ◽  
Author(s):  
Chun I. Yu ◽  
Christian Becker ◽  
Patrick Metang ◽  
Florentina Marches ◽  
Yuanyuan Wang ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Cd4 T Cells ◽  
Type 2 Cytokines

Ligation of CD2 Provides a Strong Helper Signal for the Production of the Type 2 Cytokines Interleukin-4 and -5 by Memory T Cells

1997 ◽  
Vol 181 (1) ◽  
pp. 76-85 ◽  
Author(s):  
Xiaohui Peng ◽  
Ahmad Kasran ◽  
Dominique Bullens ◽  
Jan L. Ceuppens
Keyword(s):  
T Cells ◽  
Memory T Cells ◽  
Interleukin 4 ◽  
Type 2 Cytokines

scholarly journals Type 1 and type 2 cytokine dysregulation in human infectious, neoplastic, and inflammatory diseases.

1996 ◽  
Vol 9 (4) ◽  
pp. 532-562 ◽  
Author(s):  
D R Lucey ◽  
M Clerici ◽  
G M Shearer
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Cd4 T Cells ◽  
Gamma Interferon ◽  
Human Diseases ◽  
Delayed Type Hypersensitivity ◽  
Type 2 Cytokines ◽  
Th1 And Th2

In the mid-1980s, Mosmann, Coffman, and their colleagues discovered that murine CD4+ helper T-cell clones could be distinguished by the cytokines they synthesized. The isolation of human Th1 and Th2 clones by Romagnani and coworkers in the early 1990s has led to a large number of reports on the effects of Th1 and Th2 on the human immune system. More recently, cells other than CD4+ T cells, including CD8+ T cells, monocytes, NK cells, B cells, eosinophils, mast cells, basophils, and other cells, have been shown to be capable of producing "Th1" and "Th2" cytokines. In this review, we examine the literature on human diseases, using the nomenclature of type 1 (Th1-like) and type 2 (Th2-like) cytokines, which includes all cell types producing these cytokines rather than only CD4+ T cells. Type 1 cytokines include interleukin-2 (IL-2), gamma interferon, IL-12 and tumor necrosis factor beta, while type 2 cytokines include IL-4, IL-5, IL-6, IL-10, and IL-13. In general, type 1 cytokines favor the development of a strong cellular immune response whereas type 2 cytokines favor a strong humoral immune response. Some of these type 1 and type 2 cytokines are cross-regulatory. For example, gamma interferon and IL-12 decrease the levels of type 2 cytokines whereas IL-4 and IL-10 decrease the levels of type 1 cytokines. We use this cytokine perspective to examine human diseases including infections due to viruses, bacteria, parasites, and fungi, as well as selected neoplastic, atopic, rheumatologic, autoimmune, and idiopathic-inflammatory conditions. Clinically, type 1 cytokine-predominant responses should be suspected in any delayed-type hypersensitivity-like granulomatous reactions and in infections with intracellular pathogens, whereas conditions involving hypergammaglobulinemia, increased immunoglobulin E levels, and/or eosinophilia are suggestive of type 2 cytokine-predominant conditions. If this immunologic concept is relevant to human diseases, the potential exists for novel cytokine-based therapies and novel cytokine-directed preventive vaccines for such diseases.

scholarly journals Interleukin-10- and Transforming Growth Factor β-Independent Regulation of CD8+T Cells Expressing Type 1 and Type 2 Cytokines in Human Lymphatic Filariasis

2014 ◽  
Vol 21 (12) ◽  
pp. 1620-1627 ◽  
Author(s):  
Rajamanickam Anuradha ◽  
Parakkal Jovvian George ◽  
Paul Kumaran ◽  
Thomas B. Nutman ◽  
Subash Babu
Keyword(s):  
T Cells ◽  
Growth Factor ◽  
Lymphatic Filariasis ◽  
Transforming Growth Factor ◽  
Ex Vivo ◽  
Transforming Growth Factor Β ◽  
Necrosis Factor Alpha ◽  
Type 2 Cytokines

ABSTRACTLymphatic filariasis is known to be associated with diminished CD4+Th1 and elevated CD4+Th2 responses to parasite-specific antigens. The roles of cytokine-expressing CD8+T cells in immune responses to filarial infections are not well defined. To study the roles of CD8+T cells expressing type 1, type 2, and type 17 cytokines in filarial infections, we examined the frequencies of these cells in clinically asymptomatic, patently infected (INF) individuals, directlyex vivoand in response to parasite or nonparasite antigens; these frequencies were compared with the results for individuals with filarial lymphedema (i.e., clinical pathology [CP]) and those without active infection or pathology (i.e., endemic normal [EN]). INF individuals exhibited significant decreases in the frequencies of CD8+T cells expressing tumor necrosis factor alpha (TNF-α), gamma interferon (IFN-γ), and interleukin-22 (IL-22) at baseline and/or in response to filarial antigens, compared with CP and EN individuals. In contrast, the same individuals exhibited significant increases in the frequencies of CD8+T cells expressing IL-4, IL-5, IL-9, IL-13, and IL-21, compared with CP and/or EN individuals. Curative treatment resulted in significantly increased frequencies of CD8+T cells expressing IL-2 and significantly decreased frequencies of CD8+T cells expressing type 2 cytokines. Finally, the regulation of these responses appears to be independent of IL-10 and transforming growth factor β (TGF-β), since blockade of IL-10 or TGF-β signaling did not significantly alter the frequencies of type 1 or type 2 cytokine-expressing CD8+T cells. Our findings suggest that alterations in the frequencies of cytokine-expressing CD8+T cells are characteristic features of lymphatic filarial infections.

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