Regulatory T Cells and T Cell Depletion: Role of Immunosuppressive Drugs

Graves’ hyperthyroidism can be efficiently induced in susceptible mouse strains by repeated immunization with recombinant adenovirus coding the TSH receptor (TSHR). This study was designed to evaluate the role(s) played by naturally occurring CD4+CD25+ regulatory T cells in the development of Graves’ hyperthyroidism in resistant C57BL/6 and susceptible BALB/c mice. Depletion of CD4+CD25+ T cells rendered some C57BL/6 mice susceptible to induction of hyperthyroidism. Thus, hyperthyroidism developed in 30% of the CD4+CD25+ T cell-depleted C57BL/6 mice immunized with adenovirus expressing the TSHR A-subunit (AdTSHR289) vs. 0% of those immunized with AdTSHR289 alone. This immunological manipulation also enhanced disease severity in susceptible BALB/c mice, as reflected by a significant increase in mean T4 levels by CD4+CD25+ T cell depletion. The immunoenhancing effect of CD4+CD25+ T cell depletion appears to be attributable to an increase in thyroid-stimulating antibody production and/or a decrease in thyroid-blocking antibody synthesis, but not immune deviation to either T helper 1 or 2 cells. Interestingly, unlike BALB/c mice, some hyperthyroid C57BL/6 mice showed some intrathyroidal lymphocytic infiltration with follicular destruction. These results indicate that CD4+CD25+ T cells play a role in disease susceptibility and severity in adenovirus-TSHR-induced Graves’ hyperthyroidism. Overall, the imbalance between effector and regulatory T cells appears to be crucial in the pathogenesis of Graves’ disease.

Download Full-text

Role of Bcl-2 mRNA in Homeostatic Proliferation in Circulating T-Cells in Human Liver Transplant Patients after T-Cell Depletion

Journal of Surgical Research ◽

10.1016/j.jss.2005.03.008 ◽

2005 ◽

Vol 127 (2) ◽

pp. 123-130 ◽

Cited By ~ 1

Author(s):

Hiroshi Sato ◽

Kazue Ozawa ◽

Shingo Iwata ◽

Satoshi Kaihara ◽

Yasuhiro Ogura ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Liver Transplant ◽

Human Liver ◽

Cell Depletion ◽

Homeostatic Proliferation ◽

T Cell Depletion ◽

Transplant Patients ◽

Circulating T Cells

Download Full-text

Murine Antithymocyte Globulin T-Cell Depletion Is Mediated Predominantly by Macrophages, but the Fas/FasL Pathway Selectively Targets Regulatory T Cells

Transplantation Journal ◽

10.1097/tp.0b013e31822923f7 ◽

2011 ◽

Vol 92 (5) ◽

pp. 523-528 ◽

Cited By ~ 11

Author(s):

Kathleen S. Neff ◽

Susan M. Richards ◽

John M. Williams ◽

Richard D. Garman ◽

Melanie C. Ruzek

Keyword(s):

T Cells ◽

T Cell ◽

Regulatory T Cells ◽

Antithymocyte Globulin ◽

Cell Depletion ◽

T Cell Depletion

Download Full-text

Cryptococcus neoformans Δsgl1 Vaccination Requires Either CD4+ or CD8+ T Cells for Complete Host Protection

Frontiers in Cellular and Infection Microbiology ◽

10.3389/fcimb.2021.739027 ◽

2021 ◽

Vol 11 ◽

Author(s):

Tyler G. Normile ◽

Antonella Rella ◽

Maurizio Del Poeta

Keyword(s):

T Cells ◽

T Cell ◽

Cryptococcus Neoformans ◽

Vaccine Development ◽

Cell Depletion ◽

T Cell Depletion ◽

Host Protection ◽

Life Threatening ◽

Th1 Cytokines

Cryptococcus neoformans is a fungal pathogen causing life-threatening meningoencephalitis in susceptible individuals. Fungal vaccine development has been hampered by the fact that cryptococcosis occurs during immunodeficiency. We previously reported that a C. neoformans mutant (Δsgl1) accumulating sterylglucosides (SGs) is avirulent and provides complete protection to WT challenge, even under CD4+ T cell depletion, an immunodeficient condition commonly associated with cryptococcosis. We found high levels of SGs in the lungs post-immunization with Δsgl1 that decreased upon fungal clearance. Th1 cytokines increased whereas Th2 cytokines concurrently decreased, coinciding with a large recruitment of leukocytes to the lungs. Depletion of B or CD8+ T cells did not affect either Δsgl1 clearance or protection from WT challenge. Although CD4+ T cell depletion affected clearance, mice were still protected indicating that clearance of the mutant was not necessary for host protection. Protection was lost only when both CD4+ and CD8+ T cells were depleted, highlighting a previously unexplored role of fungal-derived SGs as an immunoadjuvant for host protection against cryptococcosis.

Download Full-text

Human α1-Antitrypsin and Temporary T Cell Depletion Synergize to Expand Regulatory T Cells and to Extend Allogeneic Skin Graft Survival.

Transplantation Journal ◽

10.1097/00007890-201407151-01094 ◽

2014 ◽

Vol 98 ◽

pp. 339

Author(s):

B. Baranovski ◽

D. Ochayon ◽

E. Lewis

Keyword(s):

T Cells ◽

T Cell ◽

Regulatory T Cells ◽

Graft Survival ◽

Skin Graft ◽

Cell Depletion ◽

T Cell Depletion

Download Full-text

Thymic Regulatory T Cell Development: Role of Signalling Pathways and Transcription Factors

Clinical and Developmental Immunology ◽

10.1155/2013/617595 ◽

2013 ◽

Vol 2013 ◽

pp. 1-8 ◽

Cited By ~ 9

Author(s):

Mark Engel ◽

Tom Sidwell ◽

Ajithkumar Vasanthakumar ◽

George Grigoriadis ◽

Ashish Banerjee

Keyword(s):

T Cells ◽

Transcription Factors ◽

T Cell ◽

Regulatory T Cells ◽

Immune Tolerance ◽

Regulatory T Cell ◽

T Cell Development ◽

Signalling Pathways ◽

Treg Development

Regulatory T cells (Tregs) are a subset of CD4 T cells that are key mediators of immune tolerance. Most Tregs develop in the thymus. In this review we summarise recent findings on the role of diverse signalling pathways and downstream transcription factors in thymic Treg development.

Download Full-text

The Role of T Cell Depletion in Bone Marrow Transplantation

Allogeneic Stem Cell Transplantation ◽

10.1007/978-1-59259-333-0_21 ◽

2003 ◽

pp. 327-342

Author(s):

Yair Reisner ◽

Massimo E. Martelli

Keyword(s):

Bone Marrow ◽

Bone Marrow Transplantation ◽

T Cell ◽

Marrow Transplantation ◽

Cell Depletion ◽

T Cell Depletion

Download Full-text

Human bone marrow and peripheral blood T lymphocyte depletion: efficacy and effects of both T cells and monocytes on growth of hematopoietic progenitors

Blood ◽

10.1182/blood.v65.3.663.bloodjournal653663 ◽

1985 ◽

Vol 65 (3) ◽

pp. 663-679

Author(s):

L Levitt ◽

TJ Kipps ◽

EG Engleman ◽

PL Greenberg

Keyword(s):

T Cells ◽

T Cell ◽

T Lymphocyte ◽

Peripheral Blood ◽

Cell Depletion ◽

Target Cells ◽

Facs Analysis ◽

Hematopoietic Progenitors ◽

T Cell Depletion

The efficacy of four separate methods of human bone marrow T lymphocyte depletion was assessed, and the effect of T cells and monocytes on in vitro growth of marrow (CFU-GEMM, BFU-E, and CFU-GM) and peripheral blood (BFU-E) hematopoietic progenitors was determined. Extent of T cell depletion was assessed by multiparameter fluorescent cell sorter (FACS) analysis and by functional studies. Cells staining positively by FACS analysis for one or more of three separate fluorescent pan-T cell monoclonal antibodies (MCAbs) comprised 8.4% to 9.5% of control marrow mononuclear cells (MNCs). T cells constituted 3.2% to 5.1% of marrow following single, sequential, or combination treatment with two different pan-T cell MCAbs (Leu 1 and TM1) plus complement, 1.5% to 2.2% of marrow following solid-phase immunoabsorption (“panning”), 0.2% of marrow after sheep cell rosetting, and only 0.05% of marrow after FACS selective cell sorting and gated separation. T cells made up 59% to 73% of control peripheral blood MNCs and 0.8% to 2.8% of peripheral MNCs following sheep cell rosetting plus treatment with Leu 1 MCAb and complement. Mitogen (PHA, Con A) and allogeneic MLC-induced blastogenic responses (stimulation indices, experimental/control or E/C) revealed a concordant decrement in marrow T cell function after MCAb plus complement (E/C of 3.9 to 9.0), after panning (E/C of 1.6 to 3.5) and after sheep cell rosetting (E/C of 0.7 to 1.3), compared with control marrow (E/C of 5.3 to 15.7). After T cell depletion, marrow BFU-E growth was 95% to 120% of control, CFU-GM growth was 90% to 108% of control, and CFU-GEMM growth was 89% to 111% of control. Marrow T cell and/or monocyte depletion did not alter erythropoietin-dependent BFU-E growth in the absence of Mo-conditioned medium (81% to 95% of control), and the addition of as many as 50 to 100 X 10(3) purified marrow monocytes or T cells to 10(5) autologous nonadherent T cell-depleted marrow target cells had a negligible (P greater than .1) effect on marrow BFU-E growth in vitro. Peripheral blood (PB) BFU-E/10(5) T- depleted target cells were 106% +/- 19% of expected; PB BFU-E growth was significantly diminished after monocyte depletion alone (7% +/- 6% of expected) or after monocyte plus T cell depletion (8% +/- 4% of expected).(ABSTRACT TRUNCATED AT 400 WORDS)

Download Full-text