Restricted gamma delta T-cell receptor repertoire in IgA nephropathy renalbiopsies

Background. We have previously reported that gamma delta T cells are involv ed in the progression of IgA nephropathy (IgAN) to renal failure. Our curre nt study examined the diversity of the CDR3 region of the gamma delta T-cel l receptor (TCR), and characterized the junctional sequences of gamma delta chain TCR transcripts from T cells infiltrating renal biopsies from patien ts with IgAN and in peripheral blood T cells (PBLs) from the same patients. Method. RNA extracted from renal biopsies and PBLs of IgAN patients (N = 15 ) was transcribed and then amplified with primers specific for the four V g amma and six V delta families. Controls were renal biopsies from thin basem ent membrane disease (N = 6) and a sample from a kidney with suppurative py elonephritis. CDR3 length spectratyping and sequencing of TCR gamma delta - chain were used to analyze the diversity of CDR3 region of these receptors. Results. CDR3 spectratyping of gamma delta TCR junctional diversity demonst rated that TCR gamma delta chains (V gamma1-3 and V delta1-3) expressed by T cells from PBLs of IgAN patients and the infected kidney showed highly di verse junctional lengths that were broadly distributed. In contrast, the ju nctional lengths of V gamma1 (V gamma2, 3, 4, 5, and 8 genes) and V delta1 transcripts in the T cells infiltrating kidneys with IgAN were much more re stricted than those of PBLs. Renal biopsies from thin basement membrane dis ease demonstrated no significant signal for any V gamma or V delta family. Sequence analysis of V gamma1 and V61 transcripts from those patients with restricted CDR3 spectratyping profiles confirmed oligoclonal expansion of g amma delta T cells infiltrating the kidneys in those IgAN patients and also revealed recurrent junctional amino acid motifs in the TCR V delta1 chain in the kidney with IgAN. Conclusion. The data show that gamma delta T cells infiltrating the kidneys of IgAN patients use a restricted subset of gamma delta T cells, indicatin g clonal expansion of individual gamma delta T cells in the kidneys with Ig AN. The feature of recurrent junctional amino acid motifs in V delta1 T cel ls may indicate antigen-driven selection.