Functional characterization of T cells differentiated in vitro from bone marrow-derived CD34 cells of psoriatic patients with family history.
BACKGROUND
The strong but complex genetic background suggests that inherent and intrinsic rather than exogenous factors have a key role in immunopathogenesis of psoriasis. It is reasonable to speculate that the dysfunctional activity of psoriatic T cells may partly originate from the abnormal haematopoietic cells.


OBJECTIVE
To test if T cells originated from haematopoietic progenitor cells in psoriasis patients display functional alternations similar to previously reported abnormalities of circulating T cells.


METHODS
Bone marrow CD34(+) haematopoietic cells were isolated from psoriatic patients with family history and healthy subjects, and differentiated into T cells in vitro in the thymic stromal co-culture system. These cells were further subjected to functional comparisons such as in vitro proliferation, secretion of cytokines such as IL-4, IL-8 and IFN-gamma, and inducing the production of C-myc, Bcl-xL, and Ki67 proteins in human keratinocytes.


RESULTS
While bone marrow-derived CD34(+) cells from both patients and healthy volunteers developed into mature T cells within weeks in the thymic environment in vitro, the differentiated T cells from psoriatic patients showed higher proliferation and stronger capacity to secret TH1 cytokines in response to streptococcal superantigen. The differentiated T cells from psoriatic patients, but not from normal controls, induced overexpression of C-myc and Ki67, but not Bcl-XL, in keratinocytes.


CONCLUSIONS
T cells differentiated from CD34(+) cells of psoriatic patients, but not normal controls, are functionally similar to psoriatic circulating T cells, suggesting that the dysfunctional activity of T cells in psoriatic patients can be traced back to the early development of haematopoietic cells.
Zhang
Kaiming
K
Department of Dermatology, Taiyuan City Centre Hospital, Affiliated to Shanxi Medical University, Taiyuan City, Shanxi Province, China.
Li
Xinhua
X
Yin
Guohua
G
Liu
Yufeng
Y
Tang
Xuyuan
X
D000328:Adult; D018952:Antigens, CD34 / Q000378:metabolism*; D001853:Bone Marrow / Q000473:pathology*; D016022:Case-Control Studies; D002454:Cell Differentiation / Q000502:physiology*; D049109:Cell Proliferation; D018920:Coculture Techniques; D005192:Family Health; D005260:Female; D006412:Hematopoietic Stem Cells / Q000276:immunology / Q000473:pathology / Q000502:physiology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D015603:Keratinocytes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D011565:Psoriasis / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology*; D017154:Stromal Cells / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology / Q000502:physiology*; D051020:bcl-X Protein / Q000378:metabolism
D018952:Antigens, CD34; C494811:BCL2L1 protein, human; D016209:Interleukin-8; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D051020:bcl-X Protein; D007371:Interferon-gamma