Association of CD40 ligand expression on HTLV-I-infected T cells and maturation of dendritic cells.
Human T lymphotropic virus type I (HTLV-I) induces HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and adult T-cell leukemia (ATL). The development of HAM/TSP is associated with rapid maturation of dendritic cells (DCs), while ATL is accomplished with their maturation defect. The DC maturation is induced by cell-to-cell contact with CD4+ T cells expressing CD40 ligand (L). We determined the influence of CD40L expressed on various HTLV-I-infected T cells on the DC maturation. Around 60% of CD4+ T cells infected with HTLV-I for 1 week, expressed CD40L molecules involved in DC maturation. DCs matured by the CD40L+ T cells activated autologous CD4+ and CD8+ T cells. HTLV-I-immortalized T-cell lines established from healthy donors consistently expressed CD40L molecules for 3 months, however, some lines lost the expression soon thereafter. Interleukin (IL)-2-independent and transformed lines lacked that expression. Furthermore, T cells obtained from HAM/TSP patients expressed CD40L molecules for at least 3 weeks, whereas T cells from ATL patients did not express that. The CD40L T cells did not induce DC maturation, and required exogenous CD40L molecules for maturation. The CD40L+ T-cell-induced maturation was blocked by anti-CD40L antibody. Therefore, the lack of CD40L expression on HTLV-I-infected T cells may be associated with the development of ATL.
Makino
M
M
Division of Human Retrovirus, Center for Chronic Viral Diseases, Faculty of Medicine, Kagoshima University, Japan. mmaki@nih.go.jp
Utsunomiya
A
A
Maeda
Y
Y
Shimokubo
S
S
Izumo
S
S
Baba
M
M
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology*; D023201:CD40 Ligand / Q000378:metabolism*; D002454:Cell Differentiation; D003713:Dendritic Cells / Q000473:pathology*; D015368:Human T-lymphotropic virus 1 / Q000472:pathogenicity*; D006801:Humans; D066298:In Vitro Techniques; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000209:etiology / Q000276:immunology / Q000473:pathology; D015493:Paraparesis, Tropical Spastic / Q000209:etiology / Q000276:immunology / Q000473:pathology
D023201:CD40 Ligand