The road to the discovery of dendritic cells, a tribute to Ralph Steinman.

While it was known by the 1960s that lymphocytes mediated adaptive immunity, it was unknown how antigens stimulated lymphocytes. Between 1967 and 1973, we reported that a rare cell type in murine spleen cells took up antigen and were obligatory for T cell dependent and independent antibody responses. We referred to them as A cells or the third cell type. In 1973, Ralph Steinman and Zanvil Cohn described a rare cell type in murine spleen cells which was phagocytic but had dendrite like protrusions; they named them dendritic cells (DCs). In 1978, Steinman reported that DC were required for mixed lymphocyte reactions. From that time until recent death, Ralph Steinman pursued relentlessly in his laboratory and through collaborations around the world the role and function of DC in immunity. In passing, using a monoclonal antibody supplied by Steinman, we showed that A cells were the same as DC.

Prevention of renal allograft rejection without immune suppression: a model to revisit.

Spectacular success in preventing renal allograft rejection in rats was obtained over 40 yr ago using only the reactants of the response: donor-type antigen and homologous antiserum directed against donor-type antigen. Tolerance was antigen specific and sustained by persistent antigen of the graft. The model has never been tested rigorously in a large species, though the rationale for why the procedures should work applies across species including humans. Confirming the results in a large species would have profound impact on research for treating multiple immune mediated diseases, in addition to providing a way for treating some transplant recipients. This is a propitious time to confirm the applicability to larger species. If successful, only the lack of imagination limits the potential impact.

Production of TH1 and TH2 cell lines and clones.

This unit describes protocols for the generation of polyclonal T(H)1 and T(H)2 cell lines from naive CD4(+) T cells as well as for generation of antigen-specific cell lines from TCR-transgenic mice and antigen-specific T cell clones from primed mice. Also described are methods for the preparation and maintenance of alloreactive murine helper T (T(H)) lymphocyte and cytotoxic T lymphocyte (CTL) clones using the limiting dilution technique, as well as derivation of T(H) clones reactive with soluble protein antigens, including a method for the selection of either T(H)1 or T(H)2 lymphocyte subsets. These two subsets of T(H) cells exhibit helper function in different ways and can be distinguished by the patterns of cytokines they synthesize. Support protocols describe a micromanipulation method for cloning T cells and a roadmap for using protocols published elsewhere in this series to assess cytokine production by T cell clones and lines.