Highly altered V beta repertoire of T cells infiltrating long-term rejected kidney allografts

• Published in: The Journal of immunology (1950) 2000-02, Vol.164 (3), p.1553-1563
• Main Authors: Gagne, K, Brouard, S, Giral, M, Sebille, F, Moreau, A, Guillet, M, Bignon, J D, Imbert, B M, Cuturi, M C, Soulillou, J P
• Format: Article
• Language: English
• Subjects: Acute Disease; Adolescent; Adult; Aged; Cell Movement - immunology; Child; Chronic Disease; Clone Cells; complementarity-determining region 3; Female; Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; Genome, Viral; Graft Rejection - immunology; Graft Rejection - metabolism; Graft Rejection - pathology; Graft Rejection - virology; Humans; Kidney Transplantation - immunology; Kidney Transplantation - pathology; Macrophages - immunology; Macrophages - pathology; Male; Middle Aged; Monocytes - immunology; Monocytes - pathology; Receptors, Antigen, T-Cell, alpha-beta - biosynthesis; Receptors, Antigen, T-Cell, alpha-beta - genetics; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; T-Lymphocyte Subsets - pathology; T-Lymphocyte Subsets - virology; Transcription, Genetic - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.164.3.1553

Chronic rejection represents a major cause of long-term kidney graft loss. T cells that are predominant in long-term rejected kidney allografts (35 +/- 10% of area infiltrate) may thus be instrumental in this phenomenon, which is likely to be dependent on the indirect pathway of allorecognition only. We have analyzed the variations in T cell repertoire usage of the V beta chain at the complementary determining region 3 (CDR3) level in 18 human kidney grafts lost due to chronic rejection. We observed a strongly biased intragraft TCR V beta usage for the majority of V beta families and also a very high percentage (55%) of V beta families exhibiting common and oligoclonal V beta-C beta rearrangements in the grafts of patients with chronic rejection associated with superimposed histologically acute lesions. Furthermore, V beta 8 and V beta 23 families exhibited common and oligoclonal V beta-J beta rearrangements in 4 of 18 patients (22%). Several CDR3 amino acid sequences were found for the common and oligoclonal V beta 8-J beta 1.4 rearrangement. Quantitative PCR showed that biased V beta transcripts were also overexpressed in chronically rejected kidneys with superimposed acute lesions. In contrast, T lymphocytes infiltrating rejected allografts with chronic rejection only showed an unaltered Gaussian-type CDR3 length distribution. This pattern suggests that late graft failure associated with histological lesions restricted to Banff-defined chronic rejection does not involve T cell-mediated injury. Thus, our observation suggests that a limited number of determinants stimulates the recipient immune system in long-term allograft failure. The possibility of a local response against viral or parenchymatous cell-derived determinants is discussed.