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G Kyriakides

Publications and source records attributed to G Kyriakides.

27 records · Page 2Linked to original sources
PubMed1981

Responses of canine lymphocytes to allogeneic and autologous Islets of Langerhans in mixed cell cultures.

Because successful allotransplantation of islets of Langerhans isolated by collagenase digestion has been difficult in many animal species, we asked whether isolated islet preparations might have tissue specific determinants conferring amplified immunogenicity in vitro. Lymphocyte proliferative responses ([(3)H]thymidine uptake) were studied in beagle dogs in mixed culture combinations of lymphocyte vs. lymphocyte (MLC) and lymphocyte vs. islet (MLIC). In five MLC responder and five nonresponder pairs, peripheral blood lymphocytes of dogs A and B were used as responding cells, and dog B x-irradiated lymphocytes (Bx), x-irradiated (or nonirradiated) islets (BI), or hepatic cells (BH) were used as stimulating cells in primary and secondary reactions. For the secondary reactions, A + Bx, A + BI, or B + BI were incubated for 9 d (A'B, A'BI, B'BI, respectively) before addition of new stimulating cells. The results showed that islets were autostimulatory, eliciting a tissue-specific lymphoproliferative response in a primary MLIC. Thus, B + BI reactivity was evident at 3,5, and 7 d in primary culture, whereas collagenase-digested liver cells, or lymphocytes obtained from collagenase-digested lymph nodes did not stimulate autologous lymphocytes. A separate reactivity was observed in the allogeneic A + BI combination in MLC responder pairs, and the peak response of A + BI at 9 d was markedly greater than that of B + BI, suggesting the presence of major histocompatibility complex lymphocyte-defined locus determinants in the islet preparations, in addition to islet-specific determinants. A secondary reaction was observed if lymphocytes were primed with islets and challenged with islets (A'BI + BI or B'BI + BI), but not if they were challenged with lymphocytes (A'BI + Bx, B'BI + Bx) or hepatic cells (A'BI + BH, B'BI + AH). Furthermore, priming of lymphocytes with autologous islets (B'BI) led to exclusion of any reactivity against allogeneic lymphocytes, i.e., B'BI suppressed A + Bx, and B'BI also markedly suppressed phytohemagglutinin-stimulated lymphoproliferative responses. Experiments were performed that excluded the possibility that the insulin levels present in the MLIC, the presence of passenger lymphocytes in the islets, or the maintenance of islets in tissue culture for 1-7 d affected the observations. These results provide evidence for the existence of alloantigens as well as tissue-specific antigens on collagenase-isolated islets of Langerhans.

Animals↗
PubMed1981

Kidney transplantation by use of splenectomy and transfusions, cadaver haplotype matching, suppressor cell assays, and T-cell monitoring.

We attempted to modulate several determinants of the host immunologic profile to improve kidney transplant survival: (1) genotype matching of the cadaver donor with the recipient, (2) assessment in recipients of living related donors (LRD) for predisposition to generate suppressor cells in mixed lymphocyte culture (MLC), (3) pretransplant splenectomy and transfusions, and (4) posttransplant immunologic monitoring. Between January, 1979, and July, 1980, 48 primary renal transplants were performed and followed up between 6 and 24 months. Pretransplant splenectomy was performed, and transfusions were administered in 38 of 48 and 48 of 48 patients, respectively. Donors and recipients of 10 of 11 cadaveric transplants were genotyped and selected for one HLA haplotype identity. All 10 proved to also be one DR antigen matches. There were no cadaveric kidney losses, but one surgical antibody to T cell subtest were used to modulate rejection therapy. The LRD group (n = 37) included 13 HLA-identical, seven haploidentical low MLC reactors, and 17 haploidentical high MLC reactors. Three deaths occurred (diabetes and myocardial infarction, stroke, and pancreatitis). A three-component coculture assay was used in the LRD group before transplantation to determine the capacity to generate specific and nonspecific MLC suppressor cells. Suppressor cells were seen in 17 patients given standard immunosuppression postoperatively without rejection episodes. However, in 20 patients incapable of generating suppressor cells, seven biopsy-proved rejection episodes occurred. There were no kidney losses, with 44 of 48 surviving recipients demonstrating normal renal function.

Adolescent↗
PubMed1980

In vitro generation of human mixed lymphocyte culture suppressor cells. I. Cellular characterization and specificity.

The mixed leukocyte culture (MLC) of peripheral blood lymphocytes (PBLs) from two prospective kidney transplant recipients and their respective donors, produced a primed cell population that functioned as suppressors. The primed cells suppressed the primary and secondary MLC when added as third components, without demonstrable cytotoxic cells. Suppressor cells were derived from the MLCs of related pairs that were genotyped to be: (1) serologically defined (SD) identical and lymphocyte-defined (LD) nonidentical, and (2) HLA (total MHC) identical. Primed cells derived from MLC of unrelated HLA nonidentical subjects also showed similar effects. Two general patterns of inhibition were observed: a marked specific suppression of the autologous responding cells and, to a lesser degree, nonspecific suppression. The T cell fraction derived from the primed suppressor population was suppressive, the cells with B cell characteristics were not suppressive. The suppressive effect of cells generated in MLC was serially monitored after kidney transplantation. The suppressive activity of the primed cells was absent in the early postoperative period (4 weeks), perhaps because of high dose immunosuppression, but later in the course suppression was evident again (2 to 5 months). Manipulation of this T suppressor cell population may prove to be of value in enhancing graft acceptance.

B-Lymphocytes↗
PubMed1975

Factors influencing morbidity and mortality of renal transplantation in a high risk population.

A group of 37 patients with 39 renal transplants were studied from January 1971 to June 1974, in which 32 were considered at high risk by well defined cardiovascular, gastrointestinal, cerebral vascular, or pulmonary disease or age categories. Three of the 37 patients have died, and two patients in the high risk group, 92 per cent. Eighty-eight per cent of the entire group have functioning kidneys at present, and 93 per cent of those in the high risk group have functioning kidneys. Evaluation of pretransplant mixed lymphocyte cultures, HL-A antigen, and immune responder status; close follow-up observation of lymphocyte culture and humoral responses by in vitro testing; and the use of antilymphoblast globulin are considered to be the reasons for the improved results.

Adult↗