Th17 Responses to Collagen Type V, kα1-Tubulin, and Vimentin Are Present Early in Human Development and Persist Throughout Life.

T helper 17 (Th17)-dependent autoimmune responses can develop after heart or lung transplantation and are associated with fibro-obliterative forms of chronic rejection; however, the specific self-antigens involved are typically different from those associated with autoimmune disease. To investigate the basis of these responses, we investigated whether removal of regulatory T cells or blockade of function reveals a similar autoantigen bias. We found that Th17 cells specific for collagen type V (Col V), kα1-tubulin, and vimentin were present in healthy adult peripheral blood mononuclear cells, cord blood, and fetal thymus. Using synthetic peptides and recombinant fragments of the Col V triple helical region (α1[V]), we compared Th17 cells from healthy donors with Th17 cells from Col V-reactive heart and lung patients. Although the latter responded well to α1(V) fragments and peptides in an HLA-DR-restricted fashion, Th17 cells from healthy persons responded in an HLA-DR-restricted fashion to fragments but not to peptides. Col V, kα1-tubulin, and vimentin are preferred targets of a highly conserved, hitherto unknown, preexisting Th17 response that is MHC class II restricted. These data suggest that autoimmunity after heart and lung transplantation may result from dysregulation of an intrinsic mechanism controlling airway and vascular homeostasis.

Clinical bacteriology of cephazolin.

Cephazolin, the latest parenteral cephalosporin produced by substitution of heterocyclic groups on the 7-aminocephalosporanic acid (7-ACA) nucleus, became available for clinical use in the U.K. in 1974. Its history is traced from the original Sardinian mould (1945) through isolation of cephalosporin C (1953) and 7-ACA (1962) to its discovery (1969) and subsequent clinical use. Its mode of actionis examined and its bactericidal nature confirmed, MICs of over 500 common pathogens are used to define its spectrum. The cut-off point for sensitivity and resistance is taken as 20 mg. per l. With 30 mug. discs zone sizes less than or equal to 14mm. indicate resistance. The clinical relevance of MICs and attainable serum and urine levels is examined by relating them to clinical response in 12 patients. A disc study compares cephazolin with 4 other available cephalosporins, namely cephaloridine, cephalothinm cephalexin and cephradine. Many major discrepancies indicate that they are not interchangeable. The laboratory and clinical implications are discussed, including the need for local policy decisions regarding choice of preparation. The change from a parenteral to an oral form should be preceded by a sensitivity test against the causal organism. The validity of using a single representative disc is questioned and the use of phrases such as 'sensitive to the cephalosporins' deprecated. Cephazolin is potent, broad-spectrum and bactericidal and is potentially life-saving in serious hospital infections. The cephalosporins rival the aminoglycosides as 'best-guess' primary choice and are preferable in pregnancy, the puerperium and in pulmonary infections. Within the group cephazolin will seriously challenge or even oust cephaloridine and cephalothin.