title: Oligoclonal CD4(+) T cell expansions in lung transplant recipients with obliterative bronchiolitis.
abstract: Obliterative bronchiolitis (OB) is a dreaded and frequent complication of lung transplantation with a poorly understood immunopathogenesis. To further evaluate disease mechanisms, we used T cell antigen receptor (TCR) beta-chain variable region RNase protection assays, after polymerase chain reaction amplification of TCR cDNA, to quantitate circulating CD4(+) and CD8(+) repertoires of transplant recipients with OB or no evidence of rejection (NER). All six recipients with OB had markedly abnormal CD4 expansions (2.5 +/- 0.5 expansions/recipient) attributable to oligoclonal proliferations. Only two of six recipients with NER had a single, much lesser, CD4(+) abnormality each (p < 0.01). Moreover, one of these patients developed OB shortly thereafter, and the other NER abnormality may have predated transplantation. In contrast, CD8(+) expansions were common in both recipient populations. Findings of CD4(+) expansions had 100% sensitivity and 80% specificity for the presence or imminent development of OB. These data suggest proliferations of CD4(+) T cells are important in OB pathogenesis, and these are most likely part of a major histocompatibility complex Class II-dependent process of indirect alloantigen presentation. These CD4(+) clones are likely to have facultative helper functions for the multiple and diverse immune processes that have been implicated in OB. Furthermore, the close association of CD4(+) expansions with OB raises possibilities of development of novel diagnostic and therapeutic approaches.
authors.affiliation: Department of Immunology, Scripps Research Institute, La Jolla, CA, USA. duncsr@msx.upmc.edu
authors.forename: Steven R
authors.initials: SR
authors.lastname: Duncan
authors.forename: Colm
authors.initials: C
authors.lastname: Leonard
authors.forename: James
authors.initials: J
authors.lastname: Theodore
authors.forename: Mark
authors.initials: M
authors.lastname: Lega
authors.forename: Reda E
authors.initials: RE
authors.lastname: Girgis
authors.forename: Glenn D
authors.initials: GD
authors.lastname: Rosen
authors.forename: Argyrios N
authors.initials: AN
authors.lastname: Theofilopoulos
mesh_terms: D000328:Adult; D001707:Biopsy, Needle; D001989:Bronchiolitis Obliterans / Q000175:diagnosis / Q000276:immunology*; D015704:CD4 Antigens / Q000276:immunology*; D016516:CD4-CD8 Ratio; D002999:Clone Cells; D046508:Culture Techniques; D005260:Female; D006084:Graft Rejection / Q000209:etiology*; D006801:Humans; D016040:Lung Transplantation / Q000009:adverse effects / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology*; D012680:Sensitivity and Specificity; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014181:Transplantation Immunology; D014184:Transplantation, Homologous
chemical_list: D015704:CD4 Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta