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Functional characterization of CD4+CD25+ regulatory T cells differentiated in vitro from bone marrow‐derived haematopoietic cells of psoriasis patients with a family history of the disorder
Author(s) -
Zhang K.,
Li X.,
Yin G.,
Liu Y.,
Niu X.,
Hou R.
Publication year - 2008
Publication title -
british journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.304
H-Index - 179
eISSN - 1365-2133
pISSN - 0007-0963
DOI - 10.1111/j.1365-2133.2007.08359.x
Subject(s) - il 2 receptor , haematopoiesis , psoriasis , immunology , biology , bone marrow , interleukin 21 , cytokine , cd40 , stem cell , microbiology and biotechnology , t cell , in vitro , cytotoxic t cell , immune system , biochemistry
Summary Background In psoriasis CD4+CD25+ regulatory T cells are functionally deficient. The imbalance between regulatory and effector T‐cell functions is important for inducing psoriasis. It is reasonable to speculate that the dysfunctional activity of CD4+CD25+ regulatory cells may originate partly from the abnormal haematopoietic cells determined mainly by genetic background. Objectives To test the hypothesis that haematopoietic stem cells are responsible for dysfunctional CD4+CD25+ regulatory cells in psoriasis. Methods Bone marrow‐derived CD34+ haematopoietic cells from patients with psoriasis (with a family history of psoriasis) and from normal controls were differentiated into T cells in vitro . CD4+CD25+ T cells were isolated by an immunomagnetic bead method, and proliferation activity and capacity for cytokine secretion were determined. Furthermore, the ability of CD4+CD25+ T cells to suppress the proliferative responses of allogeneous peripheral blood CD4+CD25− effector T cells was assessed in vitro . Results The differentiated CD4+CD25+ T cells of psoriatic origin showed similar characteristics to those of normal volunteers, including proliferation activity and secretion profile of the cytokines interleukin (IL)‐2, IL‐4, IL‐8, IL‐10 and interferon (IFN)‐γ. However, proliferation and secretion levels of the cytokines IL‐2 and IL‐10 for CD4+CD25+ cells of psoriatic CD34+ cell origin were significantly lower than those of normal controls in response to streptococcal superantigen (Strep‐A). In particular, CD4+CD25+ T cells differentiated from psoriatic CD34+ cells were functionally insufficient to restrain effector T‐cell proliferation. Conclusions CD4+CD25+ T cells differentiated in vitro from haematopoietic cells of patients with psoriasis are impaired in regulatory function. The dysfunction of psoriatic CD4+CD25+ T cells may be due to inherent genetic programming passed down from bone marrow‐derived haematopoietic cells.