Production of functionally deficient dendritic cells from HTLV-I-infected monocytes: implications for the dendritic cell defect in adult T cell leukemia.
Adult T cell leukemia (ATL) is induced by an infection with human T lymphotropic virus type I (HTLV-I) and is accompanied by immunodeficiency. Monocyte-derived immature dendritic cells (DCs) donated by 11 ATL patients were suppressed in the ability to take up fluorescein isothiocyanate (FITC)-dextran and were down-regulated in the expression of CD1a and CD86 antigens (Ags). Monocytes from the patients showed impaired expression of CD14 and HLA-DR Ags. These results suggest intrinsic abnormalities of monocytes and a defect of DC maturation in ATL patients. Therefore, we examined the influence of HTLV-I infection of monocytes on their differentiation to DCs. Monocytes obtained from healthy donors were susceptible to HTLV-I infection in vitro. HTLV-I-infected monocytes were down-regulated in the expression of CD14 Ags, and immature DCs obtained from them expressed CD1a poorly and were impaired in the ability to take up FITC-dextran. Mature DCs differentiated from these cells could not stimulate autologous CD4(+) T cell or CD8(+) T cell proliferation, even after being secondarily pulsed with HTLV-I at an immature DC stage. These results suggest that HTLV-I-infected monocytes cannot properly differentiate to DCs and that this might be one of the important mechanisms producing dysfunctional DCs in ATL patients.
Makino
M
M
Division of Human Retroviruses, Center for Chronic Viral Diseases, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan. makino-m@cb3.so-net.ne.jp
Wakamatsu
S
S
Shimokubo
S
S
Arima
N
N
Baba
M
M
D000328:Adult; D002454:Cell Differentiation; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology; D015368:Human T-lymphotropic virus 1 / Q000276:immunology*; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis; D019169:Jurkat Cells; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000097:blood / Q000276:immunology*; D009000:Monocytes / Q000166:cytology / Q000276:immunology* / Q000821:virology; D010641:Phenotype
D016753:Interleukin-10