CD1-mediated gamma/delta T cell maturation of dendritic cells.
Immature myeloid dendritic cells (DCs) express only low levels of major histocompatibility complex (MHC) class II but express high levels of CD1 a, b, and c antigen-presenting molecules at the cell surface. As Vdelta1+ gamma/delta T cells are the main tissue subset of gamma/delta T cells and they are known to recognize CD1c in the absence of specific foreign antigen recognition, we examined the possible interaction of these T cells with immature DCs. We show that CD1-restricted gamma/delta T cells can mediate the maturation of DCs. DC maturation required cell-cell contact and could be blocked by antibodies against CD1c. The maturation process was partially mediated by tumor necrosis factor alpha. Importantly, immature DCs matured in the presence of lipopolysaccharide and CD1-restricted gamma/delta T cells produced bioactive interleukin-12p70. In addition, these DCs were able to efficiently present peptide antigens to naive CD4+ T cells. CD1-restricted gamma/delta T cell recognition of immature DCs provides the human immune system with the capacity to rapidly generate a pool of mature DCs early during microbial invasion. This may be an important source of critical host signals for T helper type 1 polarization of antigen-specific naive T cells and the subsequent adaptive immune response.
Leslie
David S
DS
Division of Rheumatology, Immunology and Allergy, Department of Medicine, Brigham and Women's Hospital at Harvard Medical School, Boston, MA 02115, USA.
Vincent
Michael S
MS
Spada
Franca M
FM
Das
Hiranmoy
H
Sugita
Masahiko
M
Morita
Craig T
CT
Brenner
Michael B
MB
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism; D017951:Antigen Presentation; D015703:Antigens, CD; D018949:Antigens, CD1 / Q000276:immunology / Q000378:metabolism*; D023201:CD40 Ligand / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D005434:Flow Cytometry; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000378:metabolism; D010641:Phenotype; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis*; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000097802:CD83 Antigen
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018949:Antigens, CD1; D023201:CD40 Ligand; D007136:Immunoglobulins; D007371:Interferon-gamma; D018664:Interleukin-12; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D016692:Receptors, Antigen, T-Cell, gamma-delta; D014409:Tumor Necrosis Factor-alpha; D000097802:CD83 Antigen