Human FOXN1-Deficiency Is Associated with αβ Double-Negative and FoxP3+ T-Cell Expansions That Are Distinctly Modulated upon Thymic Transplantation

Adult Renal Stem/Progenitor Cells (ARPCs) have been recently identified in the human kidney and several studies show their active role in kidney repair processes during acute or chronic injury. However, little is known about their immunomodulatory properties and their capacity to regulate specific T cell subpopulations. We co-cultured ARPCs activated by triggering Toll-Like Receptor 2 (TLR2) with human peripheral blood mononuclear cells for 5 days and 15 days and studied their immunomodulatory capacity on T cell subpopulations. We found that activated-ARPCs were able to decrease T cell proliferation but did not affect CD8+ and CD4+ T cells. Instead, Tregs and CD3+ CD4- CD8- double-negative (DN) T cells decreased after 5 days and increased after 15 days of co-culture. In addition, we found that PAI1, MCP1, GM-CSF, and CXCL1 were significantly expressed by TLR2-activated ARPCs alone and were up-regulated in T cells co-cultured with activated ARPCs. The exogenous cocktail of cytokines was able to reproduce the immunomodulatory effects of the co-culture with activated ARPCs. These data showed that ARPCs can regulate immune response by inducing Tregs and DN T cells cell modulation, which are involved in the balance between immune tolerance and autoimmunity.

Download Full-text

Disseminated Pagetoid Reticulosis Presenting as Cytotoxic CD4/CD8 Double Negative Cutaneous T-cell Lymphoma

Acta Dermato Venereologica ◽

10.1080/000155502320323388 ◽

2002 ◽

Vol 82 (4) ◽

pp. 314-316 ◽

Cited By ~ 5

Author(s):

G. Pagnanelli ◽

L. Bianchi ◽

M. Cantonetti ◽

A. Orlandi ◽

M. C. Fargnoli ◽

...

Keyword(s):

T Cell ◽

Cell Lymphoma ◽

T Cell Lymphoma ◽

Double Negative ◽

Cutaneous T Cell Lymphoma

Download Full-text

CD4+ T-Cell Converted Double Negative T-Cells Suppress B-Cells Proliferation and IGG Production in Mice.

Transplantation Journal ◽

10.1097/00007890-201407151-01283 ◽

2014 ◽

Vol 98 ◽

pp. 391

Author(s):

W. Li ◽

X. Zhao ◽

Y. Tian ◽

W. Shi ◽

X. Li ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

B Cells ◽

Cd4 T Cell ◽

Double Negative ◽

Double Negative T Cells

Download Full-text

Interleukin-4 protects double-negative and CD4 single-positive thymocytes from dexamethasone-induced apoptosis

Blood ◽

10.1182/blood.v81.5.1352.1352 ◽

1993 ◽

Vol 81 (5) ◽

pp. 1352-1358 ◽

Cited By ~ 57

Author(s):

G Migliorati ◽

I Nicoletti ◽

MC Pagliacci ◽

L D'Adamio ◽

C Riccardi

Keyword(s):

T Cell ◽

Time Course ◽

T Cell Development ◽

Cell Tumor ◽

Interleukin 4 ◽

Double Negative ◽

Phenotypic Analysis ◽

Cd8 Cells ◽

Single Positive ◽

Induced Apoptosis

Abstract Glucocorticoid hormones (GCH) and anti-CD3 monoclonal antibodies (MoAbs) induce in mouse thymocytes and T-cell tumor lines an active process of cell death called apoptosis. Interleukins (IL), including IL- 1 and IL-2, have been reported to inhibit such apoptosis. In this study we show that IL-4 also reduced the DNA fragmentation characteristic of dexamethasone (DEX)-induced apoptosis in thymocytes. This effect, studied in both time-course and dose-response experiments, was also detected at low IL-4 concentrations (1 U/mL) and against high DEX levels (10(-7) mol/L). The effect of IL-4 was blocked by an anti-IL-4 but not by an anti-IL-1 alpha MoAb, and was thus both specific and direct. Phenotypic analysis showed that IL-4 protects predominantly CD4- CD8- and CD4+CD8- cells. Our findings suggest that intrathymic T-cell development may be influenced by IL-4.

Download Full-text

Disseminated mature T-cell phenotype CD4/CD8 double-negative mycosis fungoides with pleural involvement

Hematology Transfusion and Cell Therapy ◽

10.1016/j.htct.2021.07.004 ◽

2021 ◽

Author(s):

Ganesh Kasinathan ◽

Jameela Sathar

Keyword(s):

T Cell ◽

Mycosis Fungoides ◽

Cell Phenotype ◽

Double Negative ◽

Pleural Involvement

Download Full-text

The effect of in vivo IL-7 deprivation on T cell maturation.

Journal of Experimental Medicine ◽

10.1084/jem.181.4.1399 ◽

1995 ◽

Vol 181 (4) ◽

pp. 1399-1409 ◽

Cited By ~ 91

Author(s):

S K Bhatia ◽

L T Tygrett ◽

K H Grabstein ◽

T J Waldschmidt

Keyword(s):

T Cells ◽

T Cell ◽

B Cells ◽

Present Report ◽

Critical Role ◽

Cell Maturation ◽

Double Negative ◽

Heat Stable Antigen ◽

Single Positive

A number of previous studies have suggested a key role for interleukin 7 (IL-7) in the maturation of T lymphocytes. To better assess the function of IL-7 in lymphopoiesis, we have deprived mice of IL-7 in vivo by long-term administration of a neutralizing anti-IL-7 antibody. In a previous report (Grabstein, K. H., T. J. Waldschmidt, F. D. Finkelman, B. W. Hess, A. R. Alpert, N. E. Boiani, A. E. Namen, and P. J. Morrissey. 1993. J. Exp. Med. 178:257-264), we used this system to demonstrate the critical role of IL-7 in B cell maturation. After a brief period of anti-IL-7 treatment, most of the pro-B cells and all of the pre-B and immature B cells were depleted from the bone marrow. In the present report, we have injected anti-IL-7 antibody for periods of up to 12 wk to determine the effect of in vivo IL-7 deprivation on the thymus. The results demonstrate a > 99% reduction in thymic cellularity after extended periods of antibody administration. Examination of thymic CD4- and CD8- defined subsets revealed that, on a proportional basis, the CD4+, CD8+ subset was most depleted, the CD4 and CD8 single positive cells remained essentially unchanged, and the CD4-, CD8- compartment actually increased to approximately 50% of the thymus. Further examination of the double negative thymocytes demonstrated that IL-7 deprivation did, indeed, deplete the CD3-, CD4-, CD8- precursors, with expansion of this subset being interupted at the CD44+, CD25+ stage. The proportional increase in the CD4-, CD8- compartment was found to be due to an accumulation of CD3+, T cell receptor alpha, beta + double negative T cells. Additional analysis revealed that anti-IL-7 treatment suppressed the audition/selection process of T cells, as shown by a significant reduction of single positive cells expressing CD69 and heat stable antigen. Finally, the effects of IL-7 deprivation on the thymus were found to be reversible, with a normal pattern of thymic subsets returning 4 wk after cessation of treatment. The present results thus indicate a central role for IL-7 in the maturation of thymic-derived T cells.

Download Full-text

Abstract W P87: Characteristics of T-cells Infiltrating Ruptured Intracranial Aneurysm

Stroke ◽

10.1161/str.46.suppl_1.wp87 ◽

2015 ◽

Vol 46 (suppl_1) ◽

Author(s):

Roger M Krzyzewski ◽

Magdalena K Stachura ◽

Mariusz Krupa ◽

Rafal Morga ◽

Agnieszka Sagan ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Intracranial Aneurysm ◽

Peripheral Blood ◽

Histological Finding ◽

Cell Phenotype ◽

Double Negative ◽

Activation Markers ◽

Hla Dr ◽

Ruptured Intracranial Aneurysm

Introduction: Recently the role of adaptive immunity has been implied by microarray studies. But the results are contradictory. T-cell infiltration is a frequent histological finding in ruptured IA, T-cell phenotype, characteristic and true quantitation remains unknown. We preformed a prospective study to determine the subpopulation and expression of activation markers of T-cells infiltrating ruptured IA in relation to peripheral blood. Hypothesis: IA have different subsets and activation levels of T-cells than peripheral blood. Methods: We collected the tissue of ruptured IA of 8 patients operated on within 24 hours after subarachnoid hemorrhage symptoms onset. IA tissue was digested, stained with fluorescently labeled monoclonal antibodies and submitted to flow cytometry. In addition we collected and analyzed venous blood from 6 age, sex and risk factor-matched controls. Results: CD4+ cells are less prevalent in IA tissue than in peripheral blood (42.14±17.28 vs. 65.88±5.32%; p=0.011), while there was no difference in CD8+ T-cells infiltrating IA (30.28±9.07 vs. 27.78±5.45%; p=0.585), and double negative (CD4-CD8-CD3+) T-cells were more prevalent in wall of IA than in circulation, (15.68±11.94 vs. 2.81±1.32%; p=0.026). Importantly, CD4+ infiltrating IA wall showed higher expression of HLA-DR (25.9±6.42 vs. 9.19± 3.58%; p<0.001) higher expression of CD 69 (26.8±19.66 vs. 2.73±0.93%; p=0.014). Similarly, there significantly more CD8+ cells showed HLA-DR+ in the IA than in blood. (45.96±15.57 vs. 22.47±11.46%; p=0.018) and CD69 (30.32±22.73 vs. 5.03±1.55%; p=0.022). Double negative cells in IA also had higher expression of HLA-DR (46.56±21.40 vs. 22.58±5.1%; p=0.025), CD69 (31.05±16.79 vs. 7.83±2.05%; p=0.016). Conclusion: The tissue of ruptured IA is highly infiltrated by T-cells which show high expression of activation markers such as CD69 or HLA-DR. The importance of these cells to immunopathogenesis of intracranial aneurysm rupture should be further characterized.

Download Full-text