We present the genomic sequence of Legionella pneumophila, the bacterial agent of Legionnaires' disease, a potentially fatal pneumonia acquired from aerosolized contaminated fresh water. The genome includes a 45-kilobase pair element that can exist in chromosomal and episomal forms, selective expansions of important gene families, genes for unexpected metabolic pathways, and previously unknown candidate virulence determinants. We highlight the genes that may account for Legionella's ability to survive in protozoa, mammalian macrophages, and inhospitable environmental niches and that may define new therapeutic targets.

These findings suggest that the psoriasis phenotype results from two patterns of MHC effect. The first involves the classic psoriasis susceptibility gene C*06, which confers more penetrant skin disease with less prevalent and more time-dependent musculoskeletal phenotype development. The second pattern appears to be mediated by HLA-B alleles, notably B*27, and includes temporally more coincident musculoskeletal involvement that is nearly equivalent in penetrance to that of the skin disease.

Objective To better define the immunologic character of the T cell infiltrate in lupus nephritis. Methods We performed double immunohistochemical staining and clonotypic T cell receptor (TCR) beta-chain sequencing in multiple anatomic regions isolated by laser-capture microdissection from renal biopsies. Results SLE kidneys have a variably patterned and often extensive infiltrate of predominantly clonally expanded T cells of CD4 and CD8 lineages. CD4 T cells were prominent in nearly two-thirds of SLE biopsies, and distributed as broad periglomerular aggregates or intermixed with CD8 T cells forming periglomerular caps. Sequencing of the T cell TCR from periglomerular regions showed a predominance of clonally expanded T cells. The CD8 T cells, which were present in all biopsies, often adhered to Bowman's capsule and infiltrated the tubular epithelium. They exhibited features that suggest participation in an adaptive immune response: differentiation into CD28null memory-effector phenotype, trafficking of the same expanded clonotype to different regions of the kidney and to the peripheral blood, and clonal persistence for years in repeat biopsies. CD8 T cell tubulitis was especially associated with progressive changes. Conclusions The immunological characteristics of the infiltrating CD4 and CD8 T cells in the lupus kidney indicate they have the potential to mediate injury, which may be relevant to development of progressive renal failure. Whereas the oligoclonality of the CD4 T cell infiltrate is consistent with the paradigm of SLE as a class II-associated autoimmune disease, the finding of CD8 T cell clonality and trafficking implies participation in a distinct systemic adaptive immune response.

We examined tolerance mechanisms in patients receiving HLA-mismatched combined kidney and bone marrow transplantation (CKBMT) that led to transient chimerism under a previously-published non-myeloablative conditioning regimen (Immune Tolerance Network study ITN036). Polychromatic flow cytometry (FCM) and high throughput sequencing of TCRβ hypervariable regions of DNA from peripheral blood T regulatory cells (Tregs) and CD4 non-Tregs revealed marked early enrichment of regulatory T cells (CD3+CD4+CD25highCD127lowFoxp3+) in blood that resulted from peripheral proliferation (Ki67+), possibly new thymic emigration (CD31+) and, in one tolerant subject, conversion from non-Tregs. Among recovering conventional T cells, central memory CD4+ and CD8+ cells predominated. A large fraction of the T cell clones detected in post-transplant biopsy specimens by TCR sequencing were detected in the peripheral blood and were not donor-reactive. Our results suggest that enrichment of Tregs by new thymic emigration and lymphopenia-driven peripheral proliferation in the early post-transplant period may contribute to tolerance following CKBMT. Furthermore, most conventional T cell clones detected in immunologically quiescent post-transplant biopsies appear to be circulating cells in the microvasculature rather than infiltrating T cells.