Pretransplant donor-specific helper T cell reactivity as a tool for tailoring the individual need for immunosuppression.
BACKGROUND
A reliable immunological assay for quantification of donor-specific alloreactivity to identify patients at risk for future allograft rejection would be a helpful tool in organ transplantation. Therefore, we questioned whether the T cell reactivity in patients measured before transplantation was predictive for the occurrence of acute rejection during the first year after kidney transplantation.


METHODS
The pretransplant T cell reactivity of peripheral blood mononuclear cells to donor and third-party antigens was tested in mixed lymphocyte cultures, and to tetanus toxoid. In addition, we measured the frequency of donor and third-party reactive helper T lymphocyte precursor and cytotoxic T lymphocyte precursors using limiting dilution analysis.


RESULTS
Patients who experienced acute rejection had significantly higher donor-specific mixed lymphocyte cultures responses (n=38; median stimulation index): 113 vs. 15, P=0.005) and helper T lymphocyte precursor frequency (n=37; median 194/106 vs. 62/106, P=0.009) measured before transplantation compared to patients without acute rejection. All patients with a low mixed lymphocyte culture response (stimulation index</=20; 13/13 vs. 12/25, P=0.001) and an undetectable helper T lymphocyte precursor frequency (<10/106 peripheral blood mononuclear cells; 7/7 vs. 17/30, P=0.04) before transplantation did not experience acute rejection. The donor-specific cytotoxic T lymphocyte precursor frequency (n=34; median 53/106 vs. 28/106, P=0.58) and tetanus toxoid-reactivity (n=38; median stimulation index: 53 vs.16, P=0.56) measured before transplantation did not correlate with acute rejection. No correlation between third-party reactivity and acute rejection was observed.


CONCLUSIONS
From these results we conclude that despite the current HLA matching criteria, undetectable helper T lymphocyte precursor frequency and low mixed lymphocyte culture responses against donor antigens measured before transplantation are predictive for a rejection-free first posttransplant year. These in vitro assays can be used to identify patients who require less immunosuppression after transplantation.
van der Mast
B J
BJ
University Hospital Rotterdam-Dijkzigt, Department Internal Medicine, Room Bd299, PO Box 2040, NL-3000 CA Rotterdam, The Netherlands. vandermast@inw1.azr.nl
van Besouw
N M
NM
de Kuiper
P
P
Vaessen
L M
LM
Gregoor
P J
PJ
IJzermans
J N
JN
van Gelder
T
T
Claas
F H
FH
Weimar
W
W
D000208:Acute Disease; D000328:Adult; D000368:Aged; D005260:Female; D006084:Graft Rejection / Q000209:etiology / Q000276:immunology; D006680:HLA Antigens; D006412:Hematopoietic Stem Cells / Q000276:immunology; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods*; D066298:In Vitro Techniques; D016030:Kidney Transplantation / Q000276:immunology*; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D008875:Middle Aged; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D013745:Tetanus Toxoid / Q000276:immunology; D014019:Tissue Donors
D006680:HLA Antigens; D013745:Tetanus Toxoid