Longitudinal study of the frequency of cytotoxic T cell precursors in kidney allograft recipients.
Clonal deletion or inactivation of donor-specific alloreactive cells are important mechanisms that are believed to account for acquired immune tolerance in allograft recipients. Serial assessment of precursor cytotoxic T lymphocyte frequencies (CTLpf) by limiting dilution analysis (LDA) provides information at the clonal level on changes in the alloimmune response of graft recipients. We performed a longitudinal study of 15 cadaveric kidney recipients before and every 3 months throughout the first year after transplantation (Tx). Pre-Tx values of donor CTLpf showed high interindividual variability without a predictive value for the clinical outcome. All patients with well functioning kidneys had decreased CDLpf at 3 months post-Tx in comparison with pre-Tx values. This decrease was donor-specific in four patients and was permanent in two cases throughout the study. Most patients presented decreased anti-donor CTLpf values from 6 to 9 months, whereas a partial recovery of donor CTLpf was observed in three patients. Reversible acute rejection was diagnosed in three patients, and it was associated with a marked increase in anti-donor CTLpf, returning to pre-Tx values by 9 months post-Tx. In addition, one patient with chronic rejection displayed a transient increase in CDLpf 6 months after Tx. The results of this sequential study indicate the establishment of a state of either hyporesponsiveness or functional clonal inactivation, transient or permanent, which could facilitate allograft acceptance.
Mestre
M
M
Service of Immunology, Ciutat Sanitaria i Universitaria de Bellvitge, Barcelona, Spain.
Massip
E
E
Bas
J
J
Alsina
J
J
Romeu
A
A
Castelao
A M
AM
Buendia
E
E
Grinyo
J M
JM
D000328:Adult; D017637:Clonal Deletion; D005260:Female; D006084:Graft Rejection / Q000276:immunology; D006801:Humans; D007518:Isoantibodies / Q000276:immunology; D007519:Isoantigens / Q000276:immunology; D016030:Kidney Transplantation / Q000276:immunology*; D008137:Longitudinal Studies; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D007518:Isoantibodies; D007519:Isoantigens