Ba. Yard et Fj. Vanderwoude, GRAFT-INFILTRATING CELLS CAN RECOGNIZE TISSUE-SPECIFIC ANTIGENS ON PROXIMAL TUBULAR EPITHELIAL-CELLS DURING ACUTE RENAL-ALLOGRAFT REJECTION, Infusionstherapie und Transfusionsmedizin, 25(1), 1998, pp. 30-34
The immune response during renal allograft rejection may be directed a
gainst renal-specific antigens. We conducted a study to demonstrate ti
ssue-specific recognition of proximal tubular epithelial cells (PTEC)
by graft-infiltrating cells (GIC). Both PTEC and GIC were isolated fro
m the same biopsy. Of the T cell lines generated from 25 biopsies only
5 lines showed no or low cytotoxicity against donor PTEC. Three lines
were cytotoxic towards donor PTEC, but not against PHA-stimulated spl
enocytes, suggesting tissue specificity of GIC. To study the tissue sp
ecificity more in detail we performed a limiting dilution of one of th
e tissue-specific GIC lines. We obtained 18 cytotoxic T cell (CTL) clo
nes, five of these clones were cytotoxic against donor PHA blasts, dem
onstrating not only the polyclonal nature of the T cell line, but also
that tissue specificity was not due to an intrinsic non-susceptibilit
y of PHA blasts. Nine tissue-specific clones were selected for further
analysis. All tissue-specific clones were CD8(+) and T cell receptor
(TCR) alpha/beta(+). Cytotoxicity of all clones could be inhibited wit
h CD3, CD8, anti-MHC class I and CD18 monoclonal antibody (MoAb). Only
PTEC expressing HLA-A31 were recognized by these clones. However, the
re were three clones that did not lyse all HLA-A31-expressing PTEC lin
es, suggesting recognition of a HLA-A31, tissue-associated polymorphis
m. These results show for the first time that human renal-specific ant
igens may be recognized by GIC in vitro. These GIC are likely to contr
ibute to the observed destruction of tubuli during episodes of acue re
jection.