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Title: Local and systemic induction of an abundant CD4+CD25+ regulatory T cell population in non-Hodgkin's lymphoma
Author: Mittal, Sajjan
ISNI:       0000 0004 2669 9104
Awarding Body: University of Aberdeen
Current Institution: University of Aberdeen
Date of Award: 2009
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To investigate their importance in non-Hodgkin’s lymphoma (NHL), I enumerated Treg cells in peripheral blood mononuclear cells (PBMC) and involved tissues from 30 newly diagnosed patients CD25+FoxP3+CD127lowCD4+ Treg cells were increased markedly in PBMC (median=20.4% CD4 T cells, n=20) versus healthy controls (median=3.2%, n=13: p<0.001, rank sum test) and correlated with serum lactate dehydrogenase (n=14; Rs=0.79, p<0.001) and disease stage. I documented poor proliferation of T cells with mitogen ConA and almost none with recall antigens PPD and DPT in both PBMC and involved tissue samples (n=9). T cell hyporesponsiveness was reversed by depleting CD25+ cells (n=4), or by adding anti-CDLA-4 (n=3), supporting the view that Treg cells explain the systemic immunosuppression seen in NHL. As a high percentage of Treg cells were also present in involved tissues (patients’ involved tissues median=38.8% of CD4 T cells (n=15) vs. reactive nodes median=11.6% of CD4 T cells (n=2); p=0.02, rank sum test), I determined if tumour cells could induce a T regulatory phenotype. I incubated CD25+ depleted PBMC with tumour cells in vitro for five days. A dose and time dependent T regulatory phenotype induction from CD25+ depleted PBMC fractions were seen (n=6, maximum induction of 86.7%). Partial induction was seen when these fractions were separated with transwells. These ‘induced Treg cells’ were FACS sorted and suppressed effector T cells proliferation. I conclude that NHL cells are powerful inducers of Treg cells. These cells circulate systemically and induce active immune tolerance both systematically and within tumour microenvironment, thus representing a new therapeutic target in NHL.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Lymphomas ; Cancer ; Immune response