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.