Increased usage of TCR V-beta8 in kidney transplant recipients with aberrant immune reconstitution and clinical complications

Background. The efficiency of immunosuppressive drugs prescribed after orga n transplantation is mostly monitored through clinical and biological signs of organ rejection or infection. However, it may be expected that some pat ients develop subtle alterations of their reconstituting immune system, not immediately associated with clinical events. Identification of such anomal ies could be useful to alert clinicians for possible future complications. Methods. A systematic follow-up of peripheral lymphocyte subsets, performed in a cohort of 89 kidney transplant recipients, identified severely skewed CD4/CD8 ratios in 32 patients, For 19 patients, the expression of specific T cell receptor fragments was examined using a panel of 10 monoclonal anti bodies. Abnormal control of spontaneously Epstein Barr virus-infected B cel ls was tested by investigating for the generation of spontaneous lymphoblas toid cell lines in 17 cases. The incidence of rejection and infectious epis odes was monitored. Results, A bias in T cell receptor fragments usage was detected in 14/19 ca ses, involving V beta 8 in all cases. Spontaneous lymphoblastoid cell lines of Epstein Barr positive B blasts developed in 9 of 17 cases. Eleven patie nts had early rejection episodes and 16 presented with viral prime-infectio n or reactivation. The incidence of rejection and infectious episodes was h igher in the group of 32 patients who developed such abnormal patterns than in the 57 who did not, Conclusion, Transient bias in the T cell receptor repertoire may be observe d during immune reconstitution after kidney transplantation, perhaps relate d to abnormal lymphocyte functions and associated to an impaired control of rejection and/or infectious agents.