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Human Langerhans cells (LCs) are highly efficient at priming cytolytic CD8+ T cells compared with dermal CD14+ dendritic cells (DCs). Here we show that dermal CD141 DCs instead prime a fraction of naïve CD8+ I cells into cells sharing the properties of type 2 cytokinesecreting CD8+ T cells (1C2). Differential expression of the CDSantagonist receptors on dermal CD14+ DCs, the Ig-like transcript (ILl) inhibitory receptors, explains the difference between the two types of DCs. Inhibition of CD8 function on LC5 inhibited cytotoxic T lymphocytes (CRs) and enhanced 1C2 generation. In addition, blocking ILT2 or ILT4 on dermal CD14+ DCs enhanced the generation of CTLs and inhibited TC2 cytokine production. Lastly, addition of soluble ILT2 and 1L14 receptors inhibited CR priming by LCs. Thus, ILT receptor expression explains the polarization of CD8+ 1-cell responses by LCs vs. dermal CD14+ DCs. [ABSTRACT FROM AUTHOR]

The glomerular filtration barrier prevents large serum proteins from being lost into the urine. It is not known, however, why the filter does not routinely dog with large proteins that enter the glomerular basement membrane (GBM). Here, we provide evidence that an active transport mechanism exists to remove immunoglobulins that accumulate at the filtration barrier. We found that FcRn, an lgG and albumin transport receptor, is expressed in podocytes and functions to internalize lgG from the GBM. Mice lacking FcRn accumulated lgG in the GBM as they aged, and tracer studies showed delayed clearance of lgG from the kidneys of FcRn-deficient mice. Supporting a role for this pathway in disease, saturating the clearance mechanism potentiated the pathogenicity of nephrotoxic sera. These studies support the idea that podocytes play an active role in removing proteins from the GBM and suggest that genetic or acquired impairment of the clearance machinery is likely to be a common mechanism promoting glomerular diseases. [ABSTRACT FROM AUTHOR]