Oligoclonal CD4(+) T cell expansions in lung transplant recipients with obliterative bronchiolitis.
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.
Duncan
Steven R
SR
Department of Immunology, Scripps Research Institute, La Jolla, CA, USA. duncsr@msx.upmc.edu
Leonard
Colm
C
Theodore
James
J
Lega
Mark
M
Girgis
Reda E
RE
Rosen
Glenn D
GD
Theofilopoulos
Argyrios N
AN
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
D015704:CD4 Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta