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At least 1,153 records · Page 64Linked to original sources
PubMed1983

Enhancement of reactivity of HLA-Cw antisera by extending the incubation time.

HLA-Cw antisera showing weak cytotoxic activity when tested at 1 1/2 hours in the conventional HLA-A,B, Cw testing procedure, were found to react better in the test using an extended incubation period of 3 hours. Of the 71 sera which were tested, 15 (21%) sera demonstrated an increase in anti-HLA-Cw reactivity against cells from donors possessing the corresponding Cw antigen. In addition, the use of B cells in the testing procedure appeared to be more favorable than T cells in the enhancement of reactivity of weak HLA-Cw antisera.

B-Lymphocytes↗
PubMed1983

Variant class II molecules from H-2 haplotypes in wild mouse populations: functional characteristics of closely related class II gene products.

Independently derived haplotypes found in wild populations of mice often express class II molecules antigenically related to specific alleles of the A molecules defined in laboratory mice. Tryptic peptide fingerprint comparisons of these antigenically related molecules indicate that they have similar, or possibly identical, primary structures in the A alpha, A beta, or both subunits. By using the Ak and Ap families of independently derived, antigenically related A molecules, we examined the effect that minor structural variations in the A molecule have on allorecognition by T lymphocytes. Data obtained indicate that a) minor structural variations in the A molecule can effect, although not always, major functional changes in allorecognition, b) changes in allorecognition are always detected when the A beta subunit contains structural variations, but not necessarily when the A alpha subunit contains structural variations, and c) more than one site in the A molecule can be recognized by alloreactive T lymphocytes. These results can be interpreted as indicating that specific sites within the A molecule are critically involved in allorecognition and that structural variations must affect these sites to elicit major changes in allorecognition.

Alleles↗
PubMed1995

Leukemia-specific allogeneic donor T cells: quantification by limiting dilution assay.

Allogeneic T cells are capable of discriminating between leukemia cells and non-malignant hematopoetic cells. This has been concluded from clinical BMT data and demonstrated by in vitro experiments. We analyzed the frequency and specificity of leukemia-reactive T cells from syngeneic and allogeneic blood donors by limiting dilution assays for interleukin-2-producing (TH1) and cytotoxic (CTLp) T cells. Target cells were leukemia blasts obtained from a patient with common ALL. Control targets were generated by EBV transformation. Effector cells were generated from the peripheral blood of the patient in remission, from his syngeneic brother and from eight healthy, HLA-mismatched volunteers. The effector cells were stimulated with leukemia cells and interleukin-2. Neither the patient nor his brother were able to generate anti-leukemic CTLp or TH1. The HLA-mismatched allogeneic donors displayed anti-leukemic CTLp frequencies with a range from 0 to 68 million. TH1 cells with anti-leukemic specificity were not detectable. We conclude that there are great inter-individual differences in the GVL potential of fully allogeneic peripheral T lymphocytes. It is possible to identify T cell lines with reactivity against leukemia blasts and non-reactivity against normal hematological cells from the same individual. These cell lines are potential effector cells for immunotherapy of human leukemia.

Blood Donors↗
PubMed1976

Cross-matching assays of cell-mediated immunity for transplant patients.

Assays of cell-mediated immunity before transplantation were performed on 34 patients who were defined as being at high risk by the presence of preformed lymphocytotoxic antibodies and/or HL-A incompatibilities at FOUR locus. Assays for cell-mediated lympholysis type I (cml I) were performed in donor serum, and for CML II in recipient serum, to assess the possible effect of blocking factors in the patients' sera. A positive (greater than 5% specific Cr release) and in particular a greater than 10% Cr release correlated strongly with graft rejection. The correlation between CML II and graft survival was unimpressive. No clinically beneficial blocking factor was demonstrable in the patients's sera in that 5 of 6 patients with a positive CML I but a negative CML II rejected their grafts. Conversely, 6 of 8 patients with a positive CML II and a negative CML I had excellent long-term courses. The use of CML I assay in the selection of grafts for patients at high risk is recommended.

Cadaver↗
PubMed1994

Bone marrow transplantation (BMT) in Europe for primary immunodeficiencies other than severe combined immunodeficiency: a report from the European Group for BMT and the European Group for Immunodeficiency.

Bone marrow (BM) transplantations performed between 1977 and 1991 at 13 European centers in 149 patients with 11 different primary immunodeficiency (ID) diseases (excluding severe combined immunodeficiency) were analyzed retrospectively. Overall survival among recipients of HLA genetically identical BM (n = 56) was 66%. Since October 1985, the date of a previous survey, a significant improvement in survival has been achieved in most ID diseases (overall survival, 81.5% v 51.7%; P < .01), primarily because of a decrease in the frequency of infectious complications. In long-term survivors, disease correction is excellent, with minimal sequelae in most patients. In 22 patients who received closely matched BM (ie, from phenotypically identical related donors, matched unrelated donors, or one HLA-ag-mismatched related donors), the survival rate (45.5%) was not significantly better than among 71 recipients of BM with 2 or 3 mismatched HLA antigens (38%). In the latter group, favorable outcome was associated with younger age, with transplantation since October 1985 (47% v 25%; P < .0001), and with a diagnosis of leukocyte adhesion deficiency. The improvement in outcome was mainly because of a higher engraftment rate and a decrease in the frequency of infections, although Epstein-Barr virus-induced B-lymphocyte proliferative disorders occurred in 16 patients (mainly those with Wiskott-Aldrich syndrome), 10 of whom died. The improvement in engraftment corresponded to the introduction of treatment in vivo with anti-LFA-1 antibody to prevent rejection of T-cell-depleted grafts (74% engraftment and 45% survival in 38 treated patients versus 37.5% and 21%, respectively, in 24 untreated patients.

Adult↗
PubMed1994

The crossmatch in renal transplantation. Evaluation of flow cytometry as a replacement for standard cytotoxicity.

Flow cytometry (FC) is increasingly being used as a crossmatch procedure in addition to the standard complement-dependent cytotoxicity (CDC) test. In fact, FC offers a number of advantages over CDC and has the potential to become the primary crossmatch technique for cadaveric donor renal transplantation. We evaluated this possibility in 230 patients crossmatched by both CDC and FC. The results showed that when the T cell crossmatch was negative by FC it was always negative by CDC, and that when the T cell results were positive by CDC (IgM antibodies excluded) they were also positive by FC. As expected, a number of tests were T cell-positive by FC but negative by CDC. A T cell CDC crossmatch was more likely to be positive when FC was positive for both T and B cells and when FC results were quantitatively higher. However, FC was unable to consistently predict a positive, dithiothreitol-resistant B cell CDC crossmatch. A policy to transplant patients with negative FC results (70% of the patients evaluated) and not to transplant sensitized patients with FC+ T cell results (10%) would allow us to make a final decision with only FC in 80% of the cases. Actual graft survival was similar for nonsensitized first-transplant candidates with positive (83%) or all patients with negative (86%) FC results. We conclude that FC is sufficient to make a final decision in most cases. Wider utilization will require improvements in the ability of FC to measure B cell antibodies and to quantitate antibodies to T cells.

B-Lymphocytes↗
PubMed1993

High frequencies of cytotoxic T cell precursors against minor histocompatibility antigens after HLA-identical BMT: absence of correlation with GVHD.

Limiting dilution analysis was used to quantify the frequency of cytotoxic T cell precursors (CTLp) against minor histocompatibility (H) antigens induced by HLA-identical BMT. The development of CTLp was monitored serially in ten patients developing either acute (n = 3), acute and chronic (n = 4) or no (n = 3) GVHD. In blood samples of patients taken shortly after BMT (< 100 days) a high frequency of anti-recipient CTLp was found (mean 1/3433). With time, this value decreased to become undetectable (< 1/500,000) beyond 400 days. This occurred also in patients still suffering from chronic GVHD. In contrast, autologous BMT did not induce any measurable recipient-reactive CTLp at any time point after BMT. In the early phase of reconstitution after BMT the frequency of CTLp against allo HLA-antigens was measured in the same patients. The absence of a consistent increase of allo-specific CTLp indicates that the kinetics of CTLp against host minor H antigens does not merely reflect an overall changed cytolytic potential shortly after BMT. These results indicate that: (1) HLA-identical BMT induces high frequencies of minor H antigen-specific CTLps detectable in the blood during the early phase of reconstitution, and (2) the frequency of recipient-reactive CTL measured in the peripheral blood is not an adequate parameter for GVHD. These data therefore challenge the clinical value of in vitro measurement of recipient-reactive CTLs in the peripheral blood after HLA-identical sibling BMT.

Acute Disease↗
PubMed1997

Crossmatching technique facilitating kidney transplantation.

Accelerated acute cellular rejection (AR) continues to be a serious problem in kidney transplantation (KT), suggesting that undetected presensitization may be encountered. The purpose of this study was to determine the most sensitive crossmatching (XM) technique to detect the preformed antibody (Ab) which may cause AR. One hundred and twenty two sera from 98 patients, on the waiting list for KT at Ramathibodi Hospital were XMed with 23 cadaveric splenic lymphocytes including 2 living related KT (LR-KT). The XM was performed by 3 different techniques namely, standard microlymphocytotoxicity test (standard NIH), antihuman globulin microlymphocytotoxicity test (AHG) and flow cytometric XM (FCXM). The XM results revealed that 8 out of 75 (10.7%) tests were negative by standard NIH, i.e., 5 tests were positive by AHG only and 1 test was positive by FCXM only and 2 tests were positive by both AHG and FCXM. In addition, the patients who had the AHG technique were not done, 5 out of 47 (10.7%) tests were also negative by standard NIH but were positive by FCXM. The sensitivity of the techniques was done by titrations of anti HLA-A2. It was found that FCXM was the most sensitive technique, followed by AHG and standard NIH, consecutively. In the retrospective study of LR-KT, case #1, the standard NIH for XM using pre-KT blood sample was negative while AHG and FCXM were strongly positive. The patient had AR at day 2 post-KT which confirmed by needle biopsy. The serum at day 11 and day 116 post-KT were tested again and were positive by the 3 techniques. Case #2, pre-KT blood sample showed negative T-XM by the 3 techniques while auto-B and B-XM were positive by standard NIH and AHG but negative by FCXM. This patient had rejection at day 16 after KT. The post-KT blood sample at day 30 showed positive auto T/B and T/B-XM by standard NIH and AHG whereas it was still negative by FCXM. It was also noted that Ab to donor B cell was better detected by standard NIH and AHG than FCXM. In conclusion, FCXM is more sensitive than standard NIH and AHG, however this technique is limited in detecting IgM T and B cell Ab. AHG technique can detect both IgG and IgM antidonor T and B cell Abs. In addition, AHG technique is more sensitive than standard NIH and does not require sophisticated equipment. AHG technique should be appropriate for routine XM, especially, in LR-KT and sensitized patients.

Cadaver↗