Quantitation of cyclosporine-sensitive and -resistant allospecific cytotoxic cells at birth.
In the absence of clinically relevant models of acute rejection we have attempted to develop an assay to measure cyclosporine-resistant allospecific cytotoxic cells in vitro, beginning at birth. The principle of limiting dilution analysis was applied to investigate umbilical cord bloods as responders. Responders were incubated for 1 h in different concentrations of cyclosporine and irradiated HLA mismatched stimulator cells from healthy adults added, followed by recombinant IL-2. After 7 days, responders were tested against three europium-labelled PHA blasts: stimulator, responder and third party. A significant number of cyclosporine-resistant allospecific cytotoxic cell precursors were found in cord blood indicating prior activation. They may have been primed in utero against non-inherited maternal HLA antigens. Cyclosporine-resistant allospecific cytotoxic cell precursors were demonstrated in human umbilical cord blood using a quantitative assay. These cells may influence the reaction to subsequent transplants.
Haque
K M
KM
University of Bristol Division of Transplantation Sciences, Southmead Hospital, Westbury-on-Trym, Bristol, UK.
Truman
C
C
Dittmer
I
I
Donaldson
C
C
Laundy
G
G
Dudley
J
J
Hows
J
J
Bradley
B A
BA
D000328:Adult; D002478:Cells, Cultured; D016572:Cyclosporine / Q000494:pharmacology*; D004351:Drug Resistance; D005312:Fetal Blood / Q000166:cytology / Q000276:immunology*; D006084:Graft Rejection / Q000276:immunology; D006650:Histocompatibility Testing; D006801:Humans; D007231:Infant, Newborn; D007376:Interleukin-2 / Q000494:pharmacology; D018448:Models, Immunological; D011994:Recombinant Proteins / Q000494:pharmacology; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology*
D007376:Interleukin-2; D011994:Recombinant Proteins; D016572:Cyclosporine