Identification and characterization of human pulmonary dendritic cells

Dendritic cells (DC) are specialized antigen-presenting cells, linking innate and adaptive immune responses, and thus play an important role in immunologically mediated diseases, including pulmonary diseases such as asthma and respiratory viral infections. Although much is known about the characteristics of lung DC in animal models, very few data concerning human lung DC are available. The goal of our study was to identify and characterize dendritic cells in human lung by preparing single-cell suspensions from surgical resection specimens and subsequent labeling with the recently developed blood dendritic cell antigen (BDCA) markers. A straightforward isolation procedure was developed to avoid phenotypical and functional changes induced by extensive purification methods. In this way, human lung DC were directly identified without the need for an additional adherence step for further purification. For the first time, we demonstrate the presence of three previously unidentified DC subsets in human lung digests: myeloid DC type 1 (BDCA1+/HLA-DR+), myeloid DC type 2 (BDCA3+/HLA-DR+), and plasmacytoid DC (BDCA2+/CD123+). The presence of CD1a+ DC in the human lung was confirmed. The identification and characterization of different human pulmonary DC subtypes is of great importance for the future development of DC-based immunotherapies.     

Synergistic convergence of microbiota-specific systemic IgG and secretory IgA

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Apparent genotype–phenotype correlation in childhood,adolescent, and adult Chediak‐Higashi syndrome

Chediak‐Higashi syndrome (CHS) is a rare autosomal recessive disorder characterized by severe immunologic defects, reduced pigmentation, bleeding tendency, and progressive neurological dysfunction. Most patients present in early childhood and die unless treated by bone marrow transplantation. About 10–15% of patients exhibit a much milder clinical phenotype and survive to adulthood, but develop progressive and often fatal neurological dysfunction. Very rare patients exhibit an intermediate adolescent CHS phenotype, presenting with severe infections in early childhood, but a milder course by adolescence, with no accelerated phase. Here, we describe the organization and genomic DNA sequence of the CHS1 gene and mutation analysis of 21 unrelated patients with the childhood, adolescent, and adult forms of CHS. In patients with severe childhood CHS, we found only functionally null mutant CHS1 alleles, whereas in patients with the adolescent and adult forms of CHS we also found missense mutant alleles that likely encode CHS1 polypeptides with partial function. Together, these results suggest an allelic genotype–phenotype relationship among the various clinical forms of CHS. © 2002 Wiley‐Liss, Inc.     

Intramuscular dendritic fibromyxolipoma: Myxoid variant of spindle cell lipoma?

Dendritic fibromyxolipoma (DFML) is an uncommon, recently described, benign soft tissue lesion that shares many clinical and pathological features with myxoid variants of spindle cell lipoma (SCL). As described, DFML is distinguished from SCL by the presence of dendritic cytoplasmic processes, abundant keloidal collagen and a prominent, often plexiform vascular pattern. We describe the first known reported case of an intramuscular DFML that occurred in the right shoulder region of a 73-year-old man. The tumor displayed the typical histopathological features of DFML but also included foci of chondroid metaplasia, a previously unreported finding. This report also discusses the differential diagnosis, particularly distinguishing DFML from SCL and myxoid liposarcoma. In view of the similarities in many clinical and pathological features between SCL and DFML, we speculate that DFML probably represents an unusual variant of myxoid SCL.     

HCV-specific CD27- CD28- memory T cells are depleted in hepatitis C virus and Schistosoma mansoni co-infection

Factors that influence the generation and maintenance of memory CD8+ T cells are not fully understood. The homeostasis of memory T cells is highly dynamic and tightly regulated by various stimuli, including cytokines and antigen-major histocompatibility complex ligands. We characterized the hepatitis C virus (HCV)-specific CD8+ T-cell responses in a cohort of HCV-infected individuals with or without Schistosoma mansoni co-infection from Egypt. We observed a significantly decreased CD27- CD28- (late differentiated) memory T-cell population in the HCV co-infected individuals compared to those with HCV infection alone. In contrast, there was no significant difference in the CD27+ CD28+ (early differentiated) memory T cells between the two groups. Analysis of human cytomegalovirus-specific CD8+ T-cell responses in the same individuals failed to reveal a similar pattern of altered memory T-cell differentiation. Thus, S. mansoni co-infection targets a specific subset of memory CD8+ T cells in HCV infection.