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Highly Altered Vb Repertoire of T Cells Infiltrating Long-Term Rejected Kidney Allografts

Abstract : 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 phenomenom, which is likely to be dependant on the indirect pathway of allorecognition only. We have analyzed the variations in T cell repertoire usage of the Vb 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␤ usage for the majority of V␤ families and also a very high percentage (55%) of Vb families exhibiting common and oligoclonal V␤-C␤ rearrangements in the grafts of patients with chronic rejection associated with superimposed histologically acute lesions. Furthermore, V␤8 and V␤23 families exhibited common and oligoclonal V␤-J␤ rearrangements in 4 of 18 patients (22%). Several CDR3 amino acid sequences were found for the common and oligoclonal V␤8-J␤1.4 rearrangement. Quantitative PCR showed that biased V␤ 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 Gaussiantype 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.
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Submitted on : Monday, September 20, 2021 - 4:25:48 PM
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Katia Gagne, Sophie Brouard, Magali Giral, Fabien Sebille, Anne Moreau, et al.. Highly Altered Vb Repertoire of T Cells Infiltrating Long-Term Rejected Kidney Allografts. Journal of Immunology, Publisher : Baltimore : Williams & Wilkins, c1950-. Latest Publisher : Bethesda, MD : American Association of Immunologists, 2000, 164 (3), pp.1553-63. ⟨10.4049/jimmunol.164.3.1553⟩. ⟨inserm-03349687⟩



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