Efficient virus transmission from dendritic cells to CD4+ T cells in response to antigen depends on close contact through adhesion molecules.
Monocyte-derived cultured dendritic cells (DCs) are potent antigen-presenting cells (APCs) and are susceptible to HIV-1Lai infection. Compared to the low level of virus production by HIV-1-infected DCs alone, a level of virus two to three orders of magnitude higher was produced by cocultivation of HIV-1-infected DCs with autologous resting CD4+ T cells in the presence of a nominal antigen. In this coculture system, direct contact of HIV-1-infected DCs with T cells was crucial for efficient virus transmission and subsequent virus production. Blocking of the LFA-1/ICAM-1 or LFA-3/CD2 interaction between these cells substantially reduced virus production, without influence or IL-2 production by activated T cells. In contrast, cell-cell transmission of HIV between non-APCs and activated T cells was not blocked by an antibody against LFA-3. Since a low level of virus production by HIV-infected DCs was upregulated by cross-linking of CD40, it was suggested that not only focal adhesion, but also mutual activation of HIV-infected DCs and T cells through adhesion molecules, may potentiate virus transmission and production and that such activation signals to HIV may be distinct from signals responsible for IL-2 production in activated T cells.
Tsunetsugu-Yokota
Y
Y
Department of Immunology, National Institute of infectious diseases, Tokyo, Japan. yyokota@nih.go.jp
Yasuda
S
S
Sugimoto
A
A
Yagi
T
T
Azuma
M
M
Yagita
H
H
Akagawa
K
K
Takemori
T
T
D017951:Antigen Presentation; D018801:CD2 Antigens / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology*; D019013:CD40 Antigens / Q000502:physiology; D018968:CD58 Antigens / Q000502:physiology*; D002448:Cell Adhesion; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology / Q000821:virology*; D004797:Enzyme-Linked Immunosorbent Assay; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology*; D008213:Lymphocyte Activation; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology*; D014779:Virus Replication
D018801:CD2 Antigens; D019013:CD40 Antigens; D018968:CD58 Antigens; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1