αβ TCR+T Cells, but Not B Cells, Promote Autoimmune Keratitis in B10 Mice Lacking γδ T Cells

Upper airway infections often lead to macroscopic changes in the architecture of the uvula. Using immunomorphometric analysis, we investigated the frequency and distribution of immune cells and of cytokine-producing cells in uvular samples. Tissue macrophages, αß T cells, γδ T cells, and B cells were, in declining order, the main cell populations. γδ T cells and B cells exhibited reciprocal localization, with almost all γδ T cells residing in the vicinity of the epithelium, and all B cells in the glandular area. The presence of cells expressing the suppressor phenotype CD8+CD28− αβ T cells is suggested. Fifteen to twenty-five percent of the immune cells expressed the down-regulatory cytokine tumor growth factor ß. Most macrophages were located subepithelially, in the vicinity of the basal lamina. The composition and cytokine profile of leukocytes in the tissue suggest that the uvula may be a site, additional to the jejunal mucosa, for induction of mucosal tolerance to inhaled and ingested antigens. Concomitantly, the uvula appears to be protected from invasion of microbial pathogens by a subepithelial barrier of macrophages and γδ T cells.

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The Relationship of Blood Lymphocytes to the Recirculating Lymphocyte Pool

Blood ◽

10.1182/blood.v91.5.1653.1653_1653_1661 ◽

1998 ◽

Vol 91 (5) ◽

pp. 1653-1661

Author(s):

William N. Andrade ◽

Miles G. Johnston ◽

John B. Hay

Keyword(s):

T Cells ◽

B Cells ◽

Lymphocyte Subsets ◽

Γδ T Cells ◽

Fluorescein Isothiocyanate ◽

Immunologic Memory ◽

Blood Lymphocytes ◽

Opposite Behavior ◽

Relationship Of ◽

The Relationship

Lymphocyte recirculation facilitates the detection and elimination of pathogens and the dissemination of immunologic memory. It is generally assumed that all small lymphocytes in the blood are actively recirculating, yet there is little quantitative data directly comparing the migration of this population with actively recirculating, lymph-derived lymphocytes. In this study blood lymphocytes were labeled with fluorescein isothiocyanate (FITC), and lymph lymphocytes were labeled with CM-DiI, reinfused intravenously, and monitored in blood and lymph. After equilibration the concentration of blood lymphocytes was several times higher in blood than in lymph, whereas lymph lymphocytes displayed the opposite behavior. This suggested that blood lymphocytes did not recirculate as efficiently as lymph lymphocytes, so we examined the following blood lymphocyte subsets in greater detail: B cells, CD4+, CD8+, and γδ T cells. Within 4 hours postinjection the percentage of FITC+CD8+ and CD4+ lymphocytes fell in the blood and remained significantly lower than the injected sample. In contrast, the concentration of FITC+ γδ T cells did not change, and the percentage of FITC+ B cells increased. These data suggest that subpopulations of B and perhaps γδ T lymphocytes in the blood do not recirculate efficiently through lymph nodes.

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T cells Mediate Progression of Load-Induced Osteoarthritis

10.1101/2020.05.20.106435 ◽

2020 ◽

Author(s):

Tibra A. Wheeler ◽

Adrien Y. Antoinette ◽

Matthew J. Kim ◽

Marjolein C. H. van der Meulen ◽

Ankur Singh

Keyword(s):

T Cells ◽

T Cell ◽

B Cells ◽

Lymph Nodes ◽

Mechanical Loading ◽

Joint Damage ◽

Γδ T Cells ◽

Cartilage Degradation ◽

T Cell Response ◽

Lymphoid Tissues

AbstractOsteoarthritis (OA) is a degenerative disease that manifests as joint damage and synovial inflammation. To date, most studies have focused on the decrease in cartilage stiffness, chondrocyte viability, and changes in matrix-degrading enzymes. With the exception of a few inflammatory cytokines and macrophages, the immune response in OA is poorly characterized, and the crosstalk of joint damage with T and B cells in local lymph nodes is unknown. Here, using an in vivo mouse model of mechanical loading of mouse tibia, we demonstrate that CD8+ T cells and subsets of CD4+ T cells, and not B cells, increase in the local lymph nodes and contribute to the progression of load-induced OA pathology. We demonstrate that T cell response is sex- and age-dependent. Mechanical loading of T cell knock-out mice that lack αβ T cell receptor carrying cells resulted in attenuation of both cartilage degradation and osteophyte formation in loaded joints, with a concomitant increase in γδ+ T cells. Restricting the migration of T cells in lymphoid tissues through the systemic treatment using Sphingosine-1-phosphate (S1P) inhibitor, decreased localization of T cells in synovium, and attenuated cartilage degradation. Our results lay the foundation of the role T cells play in the joint damage of load-induced OA and allude to the use of S1P inhibitors and T cell immunotherapies for slowing the progression of OA pathology.

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Increased numbers of CD5+ B cells and T cell receptor (TCR) γδ+ T cells are associated with younger age of onset in rheumatoid arthritis (RA)

Clinical & Experimental Immunology ◽

10.1111/j.1365-2249.1996.tb08287.x ◽

2007 ◽

Vol 103 (3) ◽

pp. 353-356 ◽

Cited By ~ 14

Author(s):

J. HASSAN ◽

G. YANNI ◽

V. HEGARTY ◽

C. FEIGHERY ◽

B. BRESNIHAN ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

T Cells ◽

T Cell ◽

B Cells ◽

T Cell Receptor ◽

Age Of Onset ◽

Γδ T Cells ◽

Cell Receptor ◽

Younger Age

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γδ T-cells alterations in the peripheral blood of high risk diabetes type 1 subjects with subclinical pancreatic B-cells impairment

Immunology Letters ◽

10.1016/s0165-2478(99)00066-8 ◽

1999 ◽

Vol 68 (2-3) ◽

pp. 289-293 ◽

Cited By ~ 5

Author(s):

Adam Krętowski ◽

Janusz Mysliwiec ◽

Małgorzata Szelachowska ◽

Dariusz Turowski ◽

Jolanta Wysocka ◽

...

Keyword(s):

T Cells ◽

B Cells ◽

High Risk ◽

Peripheral Blood ◽

Γδ T Cells ◽

Diabetes Type ◽

Diabetes Type 1 ◽

Pancreatic B Cells

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Expression of the pim-1 Protooncogene: Differential Inducibility between α/β and γδ-T Cells and B Cells

Cellular Immunology ◽

10.1006/cimm.1995.1059 ◽

1995 ◽

Vol 162 (1) ◽

pp. 123-130 ◽

Cited By ~ 8

Author(s):

Denise Wingett ◽

Diane Stone ◽

William C. Davis ◽

Nancy S. Magnuson

Keyword(s):

T Cells ◽

B Cells ◽

Γδ T Cells

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Helminth infections drive heterogeneity in human type 2 and regulatory cells

Science Translational Medicine ◽

10.1126/scitranslmed.aaw3703 ◽

2020 ◽

Vol 12 (524) ◽

pp. eaaw3703 ◽

Cited By ~ 6

Author(s):

Karin de Ruiter ◽

Simon P. Jochems ◽

Dicky L. Tahapary ◽

Koen A. Stam ◽

Marion König ◽

...

Keyword(s):

T Cells ◽

B Cells ◽

Rural Areas ◽

Regulatory Networks ◽

Γδ T Cells ◽

Immune Alteration ◽

Human Type ◽

Helminth Infections ◽

Hla Dr

Helminth infections induce strong type 2 and regulatory responses, but the degree of heterogeneity of such cells is not well characterized. Using mass cytometry, we profiled these cells in Europeans and Indonesians not exposed to helminths and in Indonesians residing in rural areas infected with soil-transmitted helminths. To assign immune alteration to helminth infection, the profiling was performed before and 1 year after deworming. Very distinct signatures were found in Europeans and Indonesians, showing expanded frequencies of T helper 2 cells, particularly CD161+ cells and ILC2s in helminth-infected Indonesians, which was confirmed functionally through analysis of cytokine-producing cells. Besides ILC2s and CD4+ T cells, CD8+ T cells and γδ T cells in Indonesians produced type 2 cytokines. Regulatory T cells were also expanded in Indonesians, but only those expressing CTLA-4, and some coexpressed CD38, HLA-DR, ICOS, or CD161. CD11c+ B cells were found to be the main IL-10 producers among B cells in Indonesians, a subset that was almost absent in Europeans. A number of the distinct immune profiles were driven by helminths as the profiles reverted after clearance of helminth infections. Moreover, Indonesians with no helminth infections residing in an urban area showed immune profiles that resembled Europeans rather than rural Indonesians, which excludes a major role for ethnicity. Detailed insight into the human type 2 and regulatory networks could provide opportunities to target these cells for more precise interventions.

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Early detrimental T-cell effects in experimental cerebral ischemia are neither related to adaptive immunity nor thrombus formation

Blood ◽

10.1182/blood-2009-10-249078 ◽

2010 ◽

Vol 115 (18) ◽

pp. 3835-3842 ◽

Cited By ~ 211

Author(s):

Christoph Kleinschnitz ◽

Nicholas Schwab ◽

Peter Kraft ◽

Ina Hagedorn ◽

Angela Dreykluft ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

B Cells ◽

Cerebral Ischemia ◽

Transgenic Mice ◽

Thrombus Formation ◽

Γδ T Cells ◽

Artery Occlusion ◽

Vessel Injury ◽

Tcr Signals

Abstract T cells contribute to the pathophysiology of ischemic stroke by yet unknown mechanisms. Mice with transgenic T-cell receptors (TCRs) and mutations in costimulatory molecules were used to define the minimal immunologic requirements for T cell–mediated ischemic brain damage. Stroke was induced in recombination activating gene 1–deficient (RAG1−/−) mice devoid of T and B cells, RAG1−/− mice reconstituted with B cells or T cells, TCR-transgenic mice bearing 1 single CD8+ (2C/RAG2, OTI/RAG1 mice) or CD4+ (OTII/RAG1, 2D2/RAG1 mice) TCR, mice lacking accessory molecules of TCR stimulation (CD28−/−, PD1−/−, B7-H1−/− mice), or mice deficient in nonclassical T cells (natural killer T [NKT] and γδ T cells) by transient middle cerebral artery occlusion (tMCAO). Stroke outcome was assessed at day 1. RAG1−/− mice and RAG1−/− mice reconstituted with B cells developed significantly smaller brain infarctions compared with controls, but thrombus formation after FeCl3-induced vessel injury was unimpaired. In contrast, TCR-transgenic mice and mice lacking costimulatory TCR signals were fully susceptible to tMCAO similar to mice lacking NKT and γδ T cells. These findings were corroborated by adoptive transfer experiments. Our data demonstrate that T cells critically contribute to cerebral ischemia, but their detrimental effect neither depends on antigen recognition nor TCR costimulation or thrombus formation.

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