title: HTLV-I-infected breast milk macrophages inhibit monocyte differentiation to dendritic cells.
abstract: Human T-cell leukemia virus type I (HTLV-I), a causative agent of adult T-cell leukemia (ATL), is transmitted from mother to child, predominantly by breastfeeding. Oral HTLV-I infection and infection early in life are associated with a subsequent risk of ATL. Although the pathogenic mechanisms of ATL remain largely unknown, the host immune system seems to play an important role in HTLV-I pathogenesis. Previous studies have shown that monocytes from ATL patients had reduced capacity for dendritic cell (DC) differentiation. Therefore, we performed the present study to clarify the mechanisms responsible for the impairment of DC differentiation using HTLV-I-infected breast milk macrophages (HTLV-BrMMø). We found that when CD14⁺ monocytes were cultured with GM-CSF and IL-4 in the presence of HTLV-BrMMø, they altered the surface phenotype of immature DCs and the stimulatory capacity of T-cell proliferation. The presence of HTLV-BrMMø significantly blocked the increased expression of CD1a, CD1b, CD11b, DC-SIGN, and HLA-DR; however, increased expression of CD1d and CD86 was observed. These effects could be partially replicated by incubation with culture supernatants from HTLV-BrMMø. The impairment of monocyte differentiation might be not due to HTLV-I infection of monocytes, but might be due to unknown soluble factors. Since other HTLV-I-infected cells exhibited similar inhibitory effects on monocyte differentiation to DCs, we speculated that HTLV-I infection might cause the production of some inhibitory cytokines in infected cells. Identifying the factors responsible for the impairment of monocyte differentiation to DCs may be helpful to understand HTLV-I pathogenesis.
authors.affiliation: Departments of Microbiology and Immunology, Nippon Medical School, Tokyo, Japan.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Inagaki
authors.forename: Megumi
authors.initials: M
authors.lastname: Takahashi
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Fukunaga
authors.forename: Hidemi
authors.initials: H
authors.lastname: Takahashi
mesh_terms: D002454:Cell Differentiation; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology; D015368:Human T-lymphotropic virus 1 / Q000472:pathogenicity*; D006801:Humans; D057131:Immune Evasion; D008264:Macrophages / Q000821:virology*; D008895:Milk, Human / Q000166:cytology* / Q000276:immunology / Q000821:virology; D009000:Monocytes / Q000166:cytology* / Q000276:immunology
chemical_list: D016207:Cytokines