Adoptive transfusion of tolerogenic dendritic cells prolongs the survival of liver allograft: a systematic review.

OBJECTIVES: To systematically review the effects of tolerogenic dendritic cells (Tol-DCs) induced by different methods on liver transplantation and their possible mechanisms of action. METHODS: PubMed and EMbase were searched for relevant articles through 31 December 2013. The effects of Tol-DCs on liver allograft survival were semiquantitatively evaluated, and the possible mechanisms by which Tol-DCs prolong graft survival were analyzed. RESULTS: Seven articles were included, and classified according to methods of induction, sources, and methods of infusing Tol-DCs. Tol-DCs induced from immature DCs (imDCs), with cytokines, and by gene modification induced liver transplant tolerance for 33.1 ± 32.5 days (2.7-fold vs. control), 26.17 ± 16.20 days (1.8-fold vs. control), and 11.7 ± 1.6 days (2.3-fold vs. control), respectively. DCs derived from recipient bone marrow, donor bone marrow, and donor spleen induced liver transplant tolerance for 51.0 ± 0.0 days (5.9-fold vs. control), 21.4 ± 26.8 days (2.4-fold vs. control), and 15.0 ± 0.0 days (2.3-fold vs. control), respectively. The primary mechanisms by which Tol-DCs induce liver transplant tolerance were the induction of T-cell hyporeactivity and Th2 differentiation. CONCLUSIONS: Tol-DCs induced by three different methods could extend liver allograft survival, with imDCs showing optimal results. The optimal infusion method was intravenous injection of 1-2 × 10(6) Tol-DC, similar to findings in renal transplantation. Tol-DCs prolonged liver transplant tolerance more than renal transplant tolerance.

Adoptive transfusion of tolerant dendritic cells prolong the survival of renal allografts: a systematic review.

OBJECTIVE: The aim of this study was to systematically review the effects of transfusing Tol-DCs induced by different methods on renal transplantation and survival time. METHOD: PubMed and EMbase were searched for relevant articles from inception to July 20(th), 2013. Renal allograft survival time was regarded as the endpoint outcome. The effects of Tol-DCs on renal transplantation were evaluated semi-quantitatively. RESULTS: Sixteen articles were included. There were three sources of Tol-DCs, including bone marrow, spleen, and thoracic duct lymph node. Rats were administrated cells intravenously and 83% of mice through the portal vein. Four subtypes of bone marrow Tol-DCs enhanced renal allograft time: immature DCs enhanced allograft survival 4.9-fold in rats and 2.0-fold in mice, gene modified DCs enhanced allograft survival 4.4-fold in rats and 2.2-fold in mice, and drug and cytokine induced enhanced allograft survival 2.9-fold and 2.7-fold, respectively, in rats. Tol-DCs from the spleen and thoracic duct lymph nodes prolonged allograft survival 2.7-fold and 1.8-fold, respectively, in rats. 1-2 × 10(6) doses of Tol-DCs extended the survival time of rats following renal transplantation. The key mechanisms by which Tol-DCs enhance allograft and overall survival included: (i) inducing T-cell hyporeactivity; (ii) reducing the effects of cytotoxic lymphocytes; and (iii) inducing Th2 differentiation. CONCLUSION: Bone marrow Tol-DCs can extend allograft survival and induce immune tolerance in fully MHC-mismatched renal transplantation in rats and mice. The effects of imDCs and gene modified Tol-DCs in mice are less marked. In conclusion, a single-injection of 1-2 × 10(6) doses of bone marrow Tol-DCs (i.v.), in combination with an immune-suppressor, a co-stimulator, and accessory cells can significantly extend renal allograft survival.

[Allogenic BMSCs reverse chimerism inducing the tolerance of xeno-skin graft in mouse model].

OBJECTIVE: To investigate the feasibility of bone marrow mesenchymal stem cells (BMSCs) in inducing immune tolerance and to establish the mouse model of reverse chimerism in xeno-skin transplantation. METHODS: The mouse model of bone marrow-chimerism was established with immuncompromised BALB/C-nu/nu female mice by receiving the transplantation of BMSCs from green fluorescent protein (GFP)-C57BL/10 male mice, the optimized chimeric time was identified by RT-PCR testing of SRY gene and immunohistochemistry measurement of GFP expression. In the experiment group, GFP-C57BL/10 male mice received the transplantation of the skin from immuncompromised BALB/C-nu/nu female mice with BMSCs bone marrow-chimerism. In the rejection group, GFP-C57BL/10 male mice received the transplantation of the skin from immuncompromised BALB/C-nu/nu female mice without BMSCs bone marrow-chimerism. In the control group, allo-transplantation of skin was performed in GFP-C57BL/10 male mice. Histological study was performed to investigate the survival rate and angiogenesis of the transplanted skin. RESULTS: The bone marrow chimeric model was established, the expressions of SRY gene and GFP protein reached the highest level at four weeks (1.22 +/- 0.10; 458.0 +/- 3.4) post-transplanted with BMSCs (10(6)), which was significantly different in comparison with those at one week, two weeks and six weeks posttransplantation(P < 0.05). Four-weeks after transplantation was further confirmed as the optimized chimeric time. The mean survival time of donor skin graft > 14 d in the experimental group, while it only was 5 d in the rejection group. CONCLUSION: The bone marrow-chimerism can be formed in the recipient by donor BMSCs transplantation, which can further induce tolerance of mice xeno-skin transplantation by reverse chimerism.

[Expressions of CXCL13, CD10 and bcl-6 in angioimmunoblastic T-cell lymphoma and peripheral T-cell lymphoma, not otherwise specified].

OBJECTIVE: To study the value of immunomarkers CXCL13, CD10, bcl-6 in pathologic diagnosis of angioimmunoblastic T-cell lymphoma (AITL). METHODS: One hundred and fifteen cases of AITL, 30 cases of peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS) and 30 cases of reactive lymph nodes with paracortical hyperplasia (RH) encountered during the period from January, 1990 to January, 2008 were retrieved from the archival files of the Department of Pathology, West China Hospital of Sichuan University, China. The morphologic features were reviewed and compared. Immunohistochemical study was performed by SP method for CXCL13, CD10, bcl-6, CD21, CD3epsilon, CD3, CD45RO, CD20 and Ki-67. TCR-gamma gene rearrangement study was also carried out. RESULTS: Regressed follicles were evident in 7.8% (9/115) of AITL cases, 6.7% (2/30) of PTCL, NOS cases and 83.3% (25/30) of RH cases, respectively. A marked increase of number of arborizing venules was shown in 98.3% (113/115) of AITL cases, 63.3% (19/30) of PTCL, NOS cases and 76.7% (23/30) of RH cases, respectively. In lymph nodes with paracortical hyperplasia, the expression of CXCL13, CD10 and bcl-6 were restricted to the germinal centers. In AITL, 96.5% (111/115) of cases showed CXCL13 expression, in contrast to 26.7% (8/30) of PTCL, NOS. Expression of CD10 and bcl-6 were found in the neoplastic cells in 50.4% (58/115) and 78.3% (90/115) of AITL, and 3.3% (1/30) and 3.3% (1/30) of PTCL, NOS, respectively. Irregular meshworks of CD21-positive follicular dendritic cells were found in all the AITL cases. Clonal TCR-gamma rearrangement was detected in 83% (83/100) of the AITL cases. CONCLUSIONS: AITL is a type of lymphoma originated from the follicular helper T cells. Detailed morphologic assessment and use of immunohistochemical markers are essential for accurate diagnosis.

[Clinicopathologic and immunophenotypic analysis of myeloid sarcoma].

OBJECTIVE: To study the clinicopathologic features of myeloid sarcoma and to evaluate the role of immunohistochemical study in diagnosis of this entity. METHODS: Eighty-two cases of myeloid sarcoma were retrieved from the archives of Department of Pathology, West China Hospital of Sichuan University during the period from January, 1990 to February, 2005. The morphologic features were reviewed and classified according to the 2001 WHO classification for hematopoietic and lymphoid tissue tumors. Immunohistochemical study using a panel of 11 antibodies was performed on 73 cases. The survival data were collected and analyzed by SPSS 10.0. RESULTS: The median age of patients was 35.5 years. The male-to-female ratio was 1.4:1. The sites of occurrence included lymph node (43.1%), skin (16.7%), nose (7.8%), soft tissue (7.8%) and bone (6.9%). Fifty-one cases (62.2%) represented myeloid sarcoma associated with an underlying myeloproliferative disorder and 25 cases (30.5%) represented solitary myeloid sarcoma. As for the morphology, 79 cases (96.3%) were granulocytic sarcoma, including 41 cases (51.9%) blastic type, 25 cases (31.6%) immature type and 13 cases (16.5%) differentiated type. The other 3 cases (3.7%) were monoblastic sarcoma. Immature eosinophils were found in 51 cases (64.6%) of granulocytic sarcoma, among which 13 cases (31.7%) were of blastic type. Immunohistochemical study showed that 95.9% cases (70/73) were positive for myeloperoxidase, 95.5% (63/66) for lysozyme, 95.2% (60/63) for CD68 (KP1), 90.8% (59/65) for leukocyte common antigen, 85.7% (54/63) for CD43, 77.8% (49/63) for CD117, 58.7% (37/63) for CD99, 54.0% (34/63) for CD15, 22.2% (14/63) for CD34, and 4.7% (3/64) for CD68 (PG-M1). Proliferation index, as demonstrated by Ki-67 positivity, was 0.49+/-0.22. Follow-up data was obtained in 59 of the 82 patients. The two- and five-year survival rates were 36.1% and 17.3% respectively. No significant prognostic factors were found in the survival analysis. CONCLUSIONS: Myeloid sarcoma may precede, develop in a background of myeloproliferative disorder or even after remission of the disease. The presence of immature eosinophils is an important morphologic clue and immunohistochemical study plays an essential role in arriving at a correct diagnosis. Immunopositivity for myeloperoxidase is specific for granulocytic differentiation, while CD68 (PG-M1)-positivity suggests monocytic differentiation. Detailed clinicopathologic correlation is also helpful.