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Biomedical subjects

David S Leslie

Publications and source records attributed to David S Leslie.

2 recordsLinked to original sources

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.

Antibodies, Monoclonal↗

CD1-dependent dendritic cell instruction.

Both microbial products and T cell factors influence dendritic cell (DC) maturation. However, it is not known which T cells are capable of interacting with DCs at the initiation of adaptive immunity, when foreign antigen-specific T cells are rare. We show here that self-reactive CD1-restricted T cells can promote DC maturation by recognizing CD1 in the absence of foreign antigens. T cell recognition of all four CD1 isoforms can trigger DC maturation, but their distinct mechanisms of costimulation lead to profound differences in concomitant interleukin 12 p70 production. Distinct CD1-reactive T cells may thus differentially direct DC development early in the immune response, thereby controlling subsequent polarization of acquired immunity.

Antigens, CD1↗