Details

Autor(en) / Beteiligte

• Mittal, Sajjan
• Marshall, Neil A.
• Duncan, Linda
• Culligan, Dominic J.
• Barker, Robert N.
• Vickers, Mark A.

Titel

Local and systemic induction of CD4+CD25+ regulatory T-cell population by non-Hodgkin lymphoma

Ist Teil von

• Blood, 2008-06, Vol.111 (11), p.5359-5370

Ort / Verlag

Washington, DC: Elsevier Inc

Erscheinungsjahr

2008

Quelle

MEDLINE

Beschreibungen/Notizen

• Regulatory T (Treg) cells contribute to immune evasion by malignancies. To investigate their importance in non-Hodgkin lymphoma (NHL), we enumerated Treg cells in peripheral blood mononuclear cells (PBMCs) and involved tissues from 30 patients. CD25+FoxP3+CD127lowCD4+ Treg cells were increased markedly in PBMCs (median = 20.4% CD4 T cells, n = 20) versus healthy controls (median = 3.2%, n = 13, P < .001) regardless of lymphoma subtype, and correlated with disease stage and serum lactate dehydrogenase (Rs = 0.79, P < .001). T-cell hyporesponsiveness was reversed by depleting CD25+ cells, or by adding anti–CTLA-4, supporting the view that Treg cells explain the systemic immunosuppression seen in NHL. A high proportion of Treg cells was also present in involved tissues (median = 38.8% CD4 T cells, n = 15) versus reactive nodes (median = 11.6%, n = 2, P = .02). When autologous CD25− PBMC fractions were incubated with tumor cells from patients (n = 6) in vitro, there was consistent strong induction and then expansion of cells with the CD4+CD25+FoxP3+ phenotype of classic “natural” Treg cells. This population was confirmed to be suppressive in function. Direct cell-cell interaction of tumor cells with CD25− PBMCs was important in Treg induction, although there was heterogeneity in the mechanisms responsible. We conclude that NHL cells are powerful inducers of Treg cells, which may represent a new therapeutic target.