Influence of psoriatic peripheral blood CD4+ T and CD8+ T lymphocytes on C-myc, Bcl-xL and Ki67 gene expression in keratinocytes.
T cells play a role in the hyperproliferation of keratinocytes, however, direct evidence on what is the main mechanism and which T-cell subset is central is still lacking. Our aim was to elucidate the role and mechanism of CD4+T and CD8+ T lymphocytes in the immunopathogenesis of lesion hyper-proliferation in psoriasis. T cell and CD4+T and CD8+ T cell subpopulations were isolated by immunomagnetic methods from peripheral blood of psoriatic patients and healthy volunteers. Keratinocytes from foreskins were incubated in the absence or presence of T cells and T cell subpopulations for 72 h. The expression of c-Myc, Bcl-xL and Ki67 proteins in keratinocytes were detected by immunohistochemical staining, and then IL-4, IL-8 and IFNgamma level in the supernatant was determined by respective ELISA. T cells of psoriatic origin induced keratinocytes to overexpress C-myc and Ki67 proteins with high amounts of IL-8 and IFN-gamma in the supernatant, while the T cells of normal origin did not. Furthermore, there was a difference in keratinocyte response to CD4+ T cells and CD8+ T cells from psoriatic patients. CD4+ T cells can secrete much higher levels of IL-8 and IFN-gamma and induced much stronger C-myc and Ki67 expression in keratinocytes, compared with CD8+ T cells. We concluded that psoriatic peripheral blood T cells and the T cell subpopulation could induce keratinocytes to over-express pro-proliferation proteins probably by secreting Th1 cytokines. T cells, especially the CD4+ T cell subpopulation, play an important role in the immunopathogenesis of lesion hyper-proliferation in psoriasis.
Li
Xinhua
X
Institute of Dermatology of Chinese PLA, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
Fan
Xing
X
Zhang
Kaiming
K
Yin
Guohua
G
Liu
Yufeng
Y
D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D015603:Keratinocytes / Q000276:immunology / Q000378:metabolism*; D019394:Ki-67 Antigen / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D011565:Psoriasis / Q000097:blood / Q000276:immunology*; D012867:Skin; D015854:Up-Regulation; D051020:bcl-X Protein / Q000235:genetics / Q000378:metabolism*
C494811:BCL2L1 protein, human; D016209:Interleukin-8; D019394:Ki-67 Antigen; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D051020:bcl-X Protein; D015847:Interleukin-4; D007371:Interferon-gamma