All-Trans Retinoik Asit (Atra) ve 1Α,25-Dihidroksivitamin D3 (Vitamin D3) ile Uyarılan Akut Miyeloid Lösemi Hücrelerinin T Hücre Yanıtları Üzerine Etkisi

Abstract

ATRA and D3 are the active metabolites of vitamin A and D, respectively. In this study, HL-60 myeloid leukemia cells were progressed through different maturation stages with ATRA, D3, LPS, and IFN-γ. For the determination of monocytic and/or granulocytic differentiation and theirfunctional differences, cell surface markers, cell morphology, cellular density, proliferation, and capacities of reactive oxygen species (ROS) and nitric oxide (NO) production were assessed. The aim of the study was to determine the expression of co-stimulatory and co-inhibitory molecules expressed by AML cells and their effects on T cell proliferation. Upon treatment with ATRA the promyelocytic/myeloblastic control HL-60 cells gained metamyelocytic morphology whereas promonocyte-like cells were abundant with D3 stimulation. CD11b and CD11c expression was significantly increased with ATRA stimulation; in addition to those markers CD14 was also induced with D3. These markers, especially CD11b, was associated with high cellular density. There was an inverse correlation between CD11b levels and cell proliferation. No prominent response to LPS was observed with these cells however stimulation with IFN-γ increased co-inhibitory B7-H1 and B7-DC, and decreased co-stimulatory B7-H2 molecules' expression. In addition, CD11b+ cells were identified to be the sub-population carrying CD86, B7-H1, and B7-DC molecules. In all differentiation groups, IFN-γ induced the expression of CD14 and HLA-DR, and especially of TLR4 in ATRA-stimulated HL-60 cells. In the co-cultures with T cells, the immune stimulatory capacity of CD11b+ HL-60 cells that were proceeded through different myeloid maturation/differentiation stages with ATRA or D3 was sustained. On the other hand, when CD11b+ cells (especially that of the D3-stimulated group) were developed in the presence of IFN-γ, CD4+ or CD8+ T cell stimulation were limited and/or suppressed.