Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective method for the treating of malignant diseases of hematopoietic system or non-malignant proliferative diseases, but the occurrence of graft-versus-host disease (GVHD) limits the success rate of hematopoietic stem cell transplantation. Moreover, chronic graft-versus-host disease (cGVHD) is the main factor affecting the long-term survival rate and life quality of recipient after hematopoietic stem cell transplantation. In this article, the latest research progress of the pathogenesis of cGVHD and related problems are reviewed from the thymus, cytokines, T lymphocyte subsets, B lymphocytes and its secreted antibody.
Chronic Disease ; Graft vs Host Disease ; immunology ; pathology ; Hematopoietic Stem Cell Transplantation ; adverse effects ; Humans ; Transplantation, Homologous

OBJECTIVETo investigate the role of Thl7 cells and the cytokine interleukin-17 (IL-17) in acute allograft rejection in mice.

METHODSMouse models of kidney transplantation were randomly divided into rejection group and isograft group. On the post-operative day (POD) 3 and 7, we tested the serum IL-17 level using enzyme-linked immunosorbent assay and measured the number of Th17 cells in the renal grafts by flow cytometry. The grafts were harvested and fixed in 10% formalin to prepare paraffin sections for routine pathological inspection.

RESULTSCompared to isograft group, the allograft group showed a significantly higher level of serum IL-17 on POD3 and POD7 (P<0.05), and the level of IL-17 is significantly higher on POD7 than on POD3 (P<0.05). The allograft group showed more infiltrating Th17 cells in the grafts on POD3 and POD7 (P<0.05), and the cell number was significantly greater on POD7 (P<0.05). Pathological examination also showed an increased severity of graft rejection with the post-transplantation time.

CONCLUSIONThl7 cells may play an important role in the development of renal graft rejection. IL-17 may serve as a potential specific indicator for predicting allograft rejection.

Animals ; Graft Rejection ; blood ; immunology ; Interleukin-17 ; blood ; Kidney Transplantation ; adverse effects ; immunology ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Th17 Cells ; immunology ; Transplantation, Homologous

OBJECTIVETo study the effect and implication of nonmyeloablative donor specific bone marrow (DSBM) infusion on the immunoreaction of liver allotransplantation.

METHODSOrthotopic liver transplantation model was used in this study. Groups were set as follows: Group I, syngeneic control (Wistar-to-Wistar); Group II, acute rejection (SD-to-Wistar); Group III, acute rejection treated with cyclosporine A (CsA) by intramuscular injection (SD-to-Wistar+CsA); Group IV, bone marrow infusion at 7 d pretransplantation followed by short-term CsA treatment (SD-to-Wistar+DSBM); Another group of short-term CsA treatment preoperatively without bone marrow infusion was also set as control. General characteristics and survival time were observed. Histological grades of rejection were determined by pathological examination. IL-2 and IFN-gamma level in peripheral blood and donor liver were detected respectively by Enzyme-Linked Immuno-Sorbent Assay (ELISA) and Western blot. Chimerism of donor cells was measured by PCR for a male-specific marker (Y-chromosome-specific sequence, Sry).

RESULTSNo signs of rejection were found in Group I. Acute rejection occurred in both Group II and the short-term CsA treated group. All the recipients died at (9-15) d posttransplantation with a median survival time of (10.7+/-0.5) d and (11.2+/-2.4) d, respectively. Only mild rejection could be seen in Group III. In Group IV, 4 out of 6 recipients had long-term survival (>100 d), the histological grade of rejection was significantly lower than that of Group II, so did the expression level of IL-2 and IFN-gamma in both peripheral blood and grafted liver. Y-chromosome-specific sequence (Sry) of male SD rats could be detected in the bone marrow, spleen and thymus of female recipients at 15 d after bone marrow infusion.

CONCLUSIONMild preconditioning nonmyeloablative donor specific bone marrow infusion can enhance chimerism formation in recipients, alleviate the rejection of liver allotransplantation and prolong survival of liver allotransplantation.

Animals ; Bone Marrow Transplantation ; immunology ; methods ; Graft Rejection ; etiology ; immunology ; prevention & control ; Liver Transplantation ; adverse effects ; immunology ; Male ; Rats ; Rats, Inbred Strains ; Rats, Wistar ; Transplantation, Homologous ; adverse effects ; immunology ; Treatment Outcome

OBJECTIVETo investigate the pathologic monitoring of intestinal graft rejection in auxiliary en-bloc liver-small bowel transplantation in pigs.

METHODSFifty outbred long-white pigs were randomized into three groups, and the auxiliary composite liver-small bowel allotransplantations were undertaken in 10 pigs in group A and group B while segment small bowel allotransplantations were undertaken in 10 pigs in group C. Group A and C were not treated with immunosuppressive drugs while group B was treated with cyclosporine A and methylprednisolone. The postoperative intestinal graft rejections were monitored by biopsy through the jejunostomy or ileuostomy on 1, 3, 5, 7, 14, 21 and 30 days after operation. Through routine management, the specimens were directly examined via optical and electronic microscope respectively.

RESULTSAs shown from pathological data, the median initial time of postoperative rejection in group A was 8 days (ranged from 7 to 12), later than that in group C (5 days:ranged from 3 to 5), P<0.05). On the 7th day postoperatively, the rejection scores in group A was 1.11+/-0.20, lower than that in group C(2.56+/-0.18, P<0.05), but higher than that in group B(0.20+/-0.13, P<0.05). Ultrastructure also showed more severe intestinal graft rejection in intestinal transplantation than that in combined transplantation. The median survival time was 9 days(ranged from 7 to 25) in group A and 12 days(ranged from 7 to 20) in group C, while all the pigs in group B lived longer than 30 days.

CONCLUSIONThe pathological assessment through the jejunostomy or ileuostomy biopsy is a convenient method to monitor the postoperative graft rejections in intestinal related transplantation.

Animals ; Female ; Graft Rejection ; prevention & control ; Graft Survival ; Intestine, Small ; pathology ; transplantation ; ultrastructure ; Liver Transplantation ; adverse effects ; immunology ; Male ; Swine ; Transplantation, Homologous

As the most important antigen present cells in the processes of post-transplant complications in vivo, dendritic cells (DCs) play an important role in graft versus host disease (GVHD), infection, and relapse. DCs have became one of the most critical problems in the transplantation immune research recently. The reconstitution kinetics of circulating DCs after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and its relationship with the post-transplant complications, even the promoter or inhibitor affecting this process are summarized in this review.
Dendritic Cells ; immunology ; Graft vs Host Disease ; immunology ; prevention & control ; Hematologic Neoplasms ; immunology ; therapy ; Hematopoietic Stem Cell Transplantation ; adverse effects ; Humans ; Infection ; immunology ; Kinetics ; Neoplasm Recurrence, Local ; immunology ; prevention & control ; Transplantation, Homologous

BACKGROUNDRenal transplantation in sensitized candidates remains a highly significant challenge worldwide. The production of panel reactive antibody (PRA) against human leukocyte antigen (HLA) is a major risk factor in presensitized recipients. The aim of this study was to evaluate the impact of HLA matching and recipients' PRA on two-year outcome in presensitized renal allograft recipients.

METHODSWe determined the percentage of panel reactivity and specificity of anti-HLA immunoglobulin (Ig) G antibodies in 73 presensitized renal allograft recipients compared with 81 unsensitized recipients (control group). HLA genotyping of both recipients and corresponding donors was performed by PCR with sequence-specific primers (PCR-SSP). We analyzed the factors influencing the early graft outcome (two-year rejection rates and survival rates of the grafts), including HLA mismatching, class and degree of panel reactivity, and target antigen of donors.

RESULTSPresensitized recipients had a worse two-year outcome than unsensitized recipients (P = 0.019 for rejection rate, P = 0.01 for survival rate). The difference in number of HLA-mismatched alleles with either 6-antigen matching (Ag M) standard or amino acid residue matching (Res M) standard was not significant between the rejection and non-rejection groups of presensitized recipients or between the graft survival group and graft loss group. Compared with the control group, recipients with both PRA-I and PRA-II antibodies had a significantly worse two-year outcome (P = 0.001 for rejection rate, P = 0.002 for survival rate). The two-year outcomes of the peak PRA >/= 50% group and its subgroup, at-transplant PRA > or = 50% group, were significantly worse compared with the control group (P = 0.025 and P = 0.001 for rejection rate, P = 0.043 and P = 0.024 for survival rate). The rejection rates of the at-transplant target antigen positive group and its subgroup, HLA-I target antigen positive group, were significantly higher than the control group (P = 0.001 and P = 0.001), target antigen negative group (P = 0.003 and P = 0.001), and peak target antigen positive with negative at-transplant target antigen group (P = 0.024 and P = 0.002). Two-year graft survival rates of the target antigen positive group and HLA-I target antigen positive group were significantly lower than the control group (P = 0.012 and P = 0.001). The two-year outcome of target antigen unknown group was similar to that of the target antigen positive group. Presensitized recipients with pre-transplant plasmapheresis or immunoadsorption (PRA prepared group) had a better but non-significant two-year outcome than the control group. However, the PRA unprepared presensitized recipients were different to the control group (P = 0.004 for rejection rate and P = 0.005 for survival rate). Hyperacute rejection (HR) occurred in three recipients with positive HLA-I target antigen and without mismatch according to Res M and in one case with positive PRA-II (for an unknown target antigen). No HR occurred in eight cases with positive HLA-II target antigens.

CONCLUSIONSPre-transplant PRA preparations might improve the access of presensitized patients to renal donors. Avoiding antigen-positive donors remains a fundamental measure in preventing HR and early rejections.

Adult ; Enzyme-Linked Immunosorbent Assay ; Female ; Graft Rejection ; immunology ; Graft Survival ; immunology ; HLA Antigens ; immunology ; Histocompatibility Testing ; Humans ; Isoantibodies ; blood ; Kidney Transplantation ; adverse effects ; immunology ; mortality ; Male ; Middle Aged ; Transplantation, Homologous ; immunology ; Treatment Outcome

Human cytomegalovirus (CMV) infection may cause life-threatening complications and lead to failure in transplantation. So, it is very important to explore the laboratory methods which can detect the CMV sufficiently early and accurately. This review discusses methodological aspects of quantitative CMV assays with emphasis on recently developed antigen detection assays and molecular biological methods.
Antigens, Viral ; blood ; Bone Marrow Transplantation ; adverse effects ; methods ; Cytomegalovirus ; immunology ; isolation & purification ; Cytomegalovirus Infections ; diagnosis ; etiology ; virology ; Humans ; Transplantation, Homologous

Preterm infants are a special group, and related severe neurological, respiratory, and digestive disorders have high disability/fatality rates. Allogeneic cell transplantation may be an effective method for the prevention and treatment of these diseases. At present, animal studies have been conducted for allogeneic cell transplantation in the treatment of hypoxic-ischemic encephalopathy, bronchopulmonary dysplasia, and necrotizing enterocolitis. The main difficulty of this technique is graft-versus-host reaction (GVHR), and successful induction of immune tolerance needs to be achieved in order to solve this problem. This article reviews the research advances in immune tolerance of allogeneic cell transplantation in preterm infants.
Apoptosis ; Cell Transplantation ; adverse effects ; Cytokines ; physiology ; Graft vs Host Reaction ; Humans ; Immune Tolerance ; Infant, Newborn ; Infant, Premature ; immunology ; Transplantation, Homologous

To explore the effects of ABO incompatibility between recipient and donor on HLA-matched nonmyeloablative allogeneic peripheral blood stem cell transplantation (NAST), a retrospective, cohort study was performed. Among 24 HLA-matched NAST, 15 were major ABO-incompatible and 9 minor. Control group included 24 HLA-matched NAST with ABO-compatible grafts. Nonmyeloablative conditioning regimens consisted of CTX, Ara-C and ATG. The patients were given cyclosporine A and mycophenolate mofetile for prophylaxis of acute GVHD. The ABO-incompatible patients received grafts depleted erythrocytes by hydroxyethyl starch (HES) sedimentation. The results showed that successful and stable engraftment was established in 23 patients. No recipient developed clinically immediate hemolysis during graft infusion, but 2 recipients experienced delayed hemolysis attributable to the ABO incompatibility. The median time of granulocyte counts >0.5 x 10(9)/L and platelet >30 x 10(9)/L was 11 and 14.9 days, respectively. In ABO major incompatible group, the onset of erythropoiesis after NAST was delayed. One out of 10 recipients with blood group "O" in this group developed pure red cell aplasia (PRCA), lasting 5 months. The acute GVHD occurred in 7 out of the 24 patients. The chronic GVHD occurred in 5 of 21 cases. Relapse was observed in 2 patients with acute leukemia. The actuarial probability of disease-free survival at 2 years was 63.3%. In conclusion, ABO-incompatible grafts for NAST have no adverse effect on engraftment, recovery of platelets, incidence of GVHD, relapse rate or survival. ABO-incompatible NAST is fairly safe if there is indication, however, the onset of erythropoiesis is delayed when major ABO mismatched.
ABO Blood-Group System ; immunology ; Blood Group Incompatibility ; Cohort Studies ; Graft Survival ; immunology ; Graft vs Host Disease ; etiology ; immunology ; prevention & control ; Humans ; Peripheral Blood Stem Cell Transplantation ; adverse effects ; methods ; Retrospective Studies ; Transplantation Conditioning ; methods ; Transplantation, Homologous

Allogeneic hematopoietic stem cell transplantation is the only curative therapy for severe beta-thalassemia. This time, the experience of utilizing HLA 2-loci mismatched sibling cord blood transplantation (CBT) in a child with severe beta-thalassemia was firstly reported in our country. A 3-year-male patient had been diagnosed with severe beta-thalassemia at 6 months of age (HbF 86.6%, HbA1 1.7%, HbA2 1.7%, beta globin gene mutation CD17, A-->T/IVS-II-654, C-->T). The patient's HLA typing was A 24,11, B 58,35 and DRB1 03,15. During a subsequent maternal pregnancy. The prenatal diagnosis for thalassemia and prenatal HLA typing analysis were performed on 18 weeks of pregnancy. The results indicated that the male fetus was a heterozygote (beta globin gene mutation N/CD17, A-->T), HLA typing was A 24,11, B 58,51 and DRB1 03,12. 120 ml cord blood was collected at time of delivery, the total numbers of nucleated cells, CFU-GM and CD34(+) cells were 1.830 x 10(9), 16.653 x 10(5) and 3.11 x 10(6), respectively. A new conditioning regimen including: hypertransfusion, continuous i.v. desferrioxamine, busulfan, cyclophosphamide, antithymocyte globulin plus hydroxyurea and fludarabine. GVHD prophylaxis comprised cyclosporin A and mycophenolate mofetil. The viability of cord blood at the time infusion was 92%, The total numbers of nucleated cells, CFU-GM and CD34(+) cells in the transfused cord blood were 12.06 x 10(7)/kg, 1.098 x 10(5)/kg, and 2.04 x 10(6)/kg, respectively. Results showed that the patient's clinical course after cord blood transplantation was unremarkable. Acute GVHD grade I developed on day 15, methylprednisolone 2 mg/kg was given to cure. Neutrophil engraftment (ANC > 0.5 x 10(9)/L) on day 17, platelet engraftment (> 50 x 10(9)/L) on day 50. The patients became independent from red blood cell transfusion since day 80 (when his hemoglobin level kept > 12.5 g/L). His beta globin gene mutation and HLA typing were all the same as the donor's analyzed on day 60 and 200. There was also a switch in blood group from A pre-transplant to O post-transplant. It is concluded that the new conditioning and GVHD prophylaxis regimens allow a successful engraftment in this case. This observation may contribute in developing UCBT as an alternative when matched sibling donors are not available.
Child, Preschool ; Cord Blood Stem Cell Transplantation ; adverse effects ; Globins ; genetics ; Graft vs Host Disease ; etiology ; HLA Antigens ; immunology ; Histocompatibility ; genetics ; immunology ; Histocompatibility Testing ; methods ; Humans ; Male ; Mutation ; Siblings ; Transplantation Tolerance ; immunology ; Transplantation, Homologous ; beta-Thalassemia ; therapy