CD28 family consists of CD28, ICOS, CTLA-4 and PD-1 molecules. The former two are activation receptors and the later two are inhibition receptors. They produce co-stimulatory signals combining with the relevant molecules in B7 family, which plays important role in T cell activation and homeostasis among T subsets. Although the mechanism of signaling by CD28 and CTLA-4 has been well studied, many questions still remain to be answered. Further investigations are required for substantiating the dual-signaling model.
Animals ; Antigens, CD ; Antigens, Differentiation ; immunology ; CD28 Antigens ; immunology ; CTLA-4 Antigen ; Humans ; Immunoglobulin Fc Fragments ; immunology ; Signal Transduction

OBJECTIVETo investigate the local cellular immune response after injection of superantigen, the highly agglutinative staphylococin (HAS), into the tumor bed after ultrasound-guided percutaneous microwave coagulation therapy (PMCT) in the liver cancer patients.

METHODSNinety-two patients with pathologically proven primary liver cancer were divided into two groups: 45 in group A were treated by PMCT alone and 47 in the group B by combined with ultrasound-guided percutaneous injection of highly agglutinative staphylococin (HAS). Before and after PMCT and HAS treatment, the patients underwent ultrasound-guided percutaneous biopsy from the tumor bed and the samples were examined by pathology and immunohistochemistry. The infiltration of CD3+, CD4+, CD57+ and CD68+ lymphocytes in treatment zone was compared between the two groups. Moreover, the infiltrating immunocytes were observed by transmission electron microscopy.

RESULTSOne week after HAS injection, the densities of CD3+, CD4+, CD57+ and CD68+ cells in the group B were 54.50 +/- 18.44, 38.14 +/- 12.44, 33.38 +/- 10.79 and 45.56 +/- 16.53, respectively. All the above mentioned parameters increased significantly in varying degrees compared with that before PMCT or HAS injection (P < 0.05). Four weeks after HAS injection, the density of CD3+, CD4+, CD57+ and CD68+ cells in the group B were 32.67 +/- 10.42, 23.43 +/- 6.99, 18.63 +/- 7.89 and 30.01 +/- 11.05, respectively, still significantly higher than those before PMCT (P < 0.05). Five weeks after PMCT and HAS injection, the densities of CD3+, CD4+, CD57+ and CD68+ cells in the group B were 54.50 +/- 18.44, 38.14 +/- 12.44, 33.38 +/- 10.79 and 45.56 +/- 16.53, versus 32.03 +/- 8.11, 15.67 +/- 8.32, 15.23 +/- 8.26 and 29.67 +/- 11.98 in the group A, respectively, still with a significant difference between the two groups (P < 0.05). A lot of lysosomes, endoplasmic reticulum and mitochondria in the immune cells after injection of HAS were observed by transmission electron microscopy.

CONCLUSIONThe local cellular immunity in liver cancer treatment area can be significantly improved by ultrasound-guided injection of highly agglutinative staphylococin after percutaneous microwave coagulation therapy.

Adult ; Aged ; Antigens, CD ; immunology ; Antigens, Differentiation, Myelomonocytic ; immunology ; CD3 Complex ; immunology ; CD4 Antigens ; immunology ; CD57 Antigens ; immunology ; Electrocoagulation ; methods ; Female ; Humans ; Liver Neoplasms ; pathology ; therapy ; Male ; Microwaves ; therapeutic use ; Middle Aged ; Superantigens ; therapeutic use ; T-Lymphocytes ; immunology

OBJECTIVETo study the clinicopathologic features, diagnosis and differential diagnosis of extramedullary infiltration of acute monocytic leukemia/monoblastic sarcoma.

METHODSFive cases of extramedullary infiltration of acute monocytic leukemia/monoblastic sarcoma were selected from 102 cases of myeloid sarcoma diagnosed during the period from 1990 to 2006. The clinicopathologic findings and followup data were retrospectively analyzed. Immunohistochemical study was also carried out with SP method.

RESULTSAmong the 5 cases studied, 3 were males and 2 were females, including 2 children and 3 adults. Generalized lymphadenopathy was found in 4 patients and skin lesions were observed in 2 patients. The tumor cells in all cases were positive for CD68 (KP1), CD68 (PGM1), lysozyme and CD45. They were negative for MPO, CD15, CD163, TdT, CD117, T and B cell markers. The Ki-67 index ranged from 40% to 80%. Follow-up data were available in all the 5 patients. Four of the 5 patients died of the disease, with the average survival time being 6.25 months.

CONCLUSIONSMonoblastic sarcoma is a rare disease with poor prognosis. It is almost impossible to distinguish monoblastic sarcoma from granulocytic sarcoma and other types of small round cell tumors on the basis of morphologic examination alone. Immunohistochemistry is mandatory for a correct diagnosis.

Adult ; Antigens, CD ; immunology ; Antigens, Differentiation, Myelomonocytic ; immunology ; Child ; Diagnosis, Differential ; Female ; Humans ; Immunohistochemistry ; methods ; Immunophenotyping ; Leukemia, Monocytic, Acute ; immunology ; pathology ; Leukocyte Common Antigens ; Lewis X Antigen ; immunology ; Male ; Receptors, Cell Surface ; immunology ; Sarcoma ; immunology ; pathology ; Sarcoma, Myeloid ; immunology ; pathology

Antigens, CD ; immunology ; Antigens, Differentiation, Myelomonocytic ; immunology ; Child, Preschool ; Diagnosis, Differential ; Histiocytes ; immunology ; pathology ; Histiocytosis, Sinus ; diagnosis ; pathology ; Humans ; Lymph Nodes ; immunology ; pathology ; Lymphatic Diseases ; diagnosis ; pathology ; Male

OBJECTIVEThe low rate of engraftment in children with beta-thalassemia has seriously restricted the popularity of the hematopoietic stem cell transplantation (HSCT). Panel reactive antibody (PRA) has been regarded as one of the important factors for the success of kidney transplantation. Poly-transfusion before transplantation is associated with the production of PRA. Also PRA is produced in the children with beta-thalassemia major who need poly-transfusion for life. PRA might be one of factors inducing the low rate of engraftment in children with beta-thalassemia. This study focused on observing the effect of PRA on the proliferation, differentiation, apoptosis and necrosis of cord blood CD34(+) cells in vitro by incubating the cord blood CD34(+) cells with serum containing PRA.

METHODSeven samples of cord blood were collected and the HLA typing for every sample was done. Seven sera positive for PRA and seven negative sera were selected respectively. Mononuclear cells (MNCs) were obtained by Ficoll-Hypaque density gradient centrifugation. CD34(+) cells were isolated from MNCs by positive selection using an immunomagnetic separation (CD34(+) progenitor cell isolation kit and auto-MACS). The CD34(+) cells of umbilical cord blood were incubated with the serum and complement in the following groups: A (absence of serum), B (presence of PRA positive serum), C (presence of PRA positive serum and complement), D (presence of complement), and E (presence of PRA negative serum). After incubation the samples were centrifuged and the supernatant was collected for LDH detection. At the same time the CD34(+) cells were harvested for assessing the expression of Annexin V and CD95 of the CD34(+) cells by flow cytometry and also for the detection of the DNA synthesis by (3)H-TaR incorporation. Meanwhile the cells were inoculated into the methylcellulose cultural system. The proliferation and hematopoietic potential of the CD34(+) cell of cord blood by the colony formation assay were detected on the day 10.

RESULTThe concentration of LDH in group A was (20.71 +/- 2.81) U/L, which was significantly lower than that in group B (64.28 +/- 5.12) U/L and group C (84.29 +/- 4.99) U/L. The concentration of LDH in group B was significantly lower than that in group C, while there were no significant differences in the concentration of LDH among groups A, D and E (P > 0.05). The cpm in group A was (22 629 +/- 3288), which was significantly higher than that in group B (4598 +/- 2178) and group C (1626 +/- 1192). And the cpm in group B was significantly higher than that in group C. There were no significant differences in the cpm among groups A, D and E (P > 0.05). On day 10 of culture, the total colonies, granulocyte-macrophage colony forming unit (CFU-GM), mixed colony forming unit (CFU-GEMM) and erythroid burst colony forming unit (BFU-E) in group A were significantly higher than that in group B and C. The total colonies, CFU-GM and CFU-GEMM in group B were significantly higher than those in group C. No significant differences were found in the total colonies, CFU-GM, CFU-GEMM and BFU-E among groups A, D and E (P > 0.05). There were no statistically significant differences in the CD95 and Annexin V expression among all the groups (P > 0.05).

CONCLUSIONPRA could impair the membrane, decrease the DNA synthesis, and inhibit the colony formation of CD34(+) cord blood cells, which could be strengthened by the presence of the complement at the given concentration in our study. PRA had no significant influence on the apoptosis of CD34(+) cells in vitro.

Antibodies ; immunology ; Antigens, CD34 ; Apoptosis ; immunology ; Cell Differentiation ; immunology ; Cell Proliferation ; Cells, Cultured ; Child ; Fetal Blood ; cytology ; immunology ; metabolism ; Flow Cytometry ; Humans ; Quorum Sensing ; immunology ; beta-Thalassemia ; immunology

The expression of inducible co-stimulator (ICOS) in peripheral blood T lymphocytes from the patients with systemic lupus erythematosus (SLE) and the role in the pathogenesis of SLE was investigated. By using two-color immunofluorescent staining and flow cytometric assay, the expression levels of ICOS in peripheal blood T lymphocytes from 33 patients with SLE and 16 healthy volunteers were detected. SLE diseases activity index (SLEDAI) of the patients with SLE was used to evaluate the disease activity. The correlation between the ICOS expression and SLEDAI was analyzed among the groups. The results showed that the expression levels of ICOS in T lymphocytes in active SLE group was markedly higher than those in the control and inactive SLE groups (both P< 0.01). There was no significant difference in the expression levels of ICOS between the inactive SLE and the control groups (P>0.05). In active SLE and inactive SLE groups, positive linear correlation was found between the levels of the ICOS expression in T lymphocytes and SLEDAI (r=0. 711, P=0.001; r=0.561, P=0.03). It was suggested that the expression of ICOS in peripheral blood T lymphocytes from the patients with active SLE was up-regulated and and ICOS might be related to the pathogenesis of SLE.
Antigens, Differentiation, T-Lymphocyte/*biosynthesis ; Antigens, Differentiation, T-Lymphocyte/genetics ; Lupus Erythematosus, Systemic/blood ; Lupus Erythematosus, Systemic/etiology ; Lupus Erythematosus, Systemic/*immunology ; T-Lymphocytes/*immunology

Animals ; Antigens, Neoplasm ; immunology ; Apoptosis ; Cell Differentiation ; Humans ; Macrophages ; pathology ; Neoplasm Regression, Spontaneous ; immunology ; pathology ; physiopathology ; Neoplasms ; immunology ; pathology

It is necessary that the two signals are required in T cells activation. The first signal is specific, which T cell receptor could recognize and bind MHC molecule by antigen-presenting cells. Another one is nonspecific, which results from CD28/B7/CTLA4 molecules on T cells and antigen-presenting cells. The both of signals regulate function of T cells such as the activation, proliferation and secreting cytokines. CTLA4 showed the up-regulation in CD28/B7 costimulatory pathway as a negative signal. The immunosuppression could occur by blocking CD28/B7 pathway. It provided useful method for immunotherapy in the autoimmune diseases and graft-versus-host disease. But then, the activation of CD28/B7 could be valuable for the immune system recognizing and eliminating tumor cells.
Abatacept ; Animals ; Antigen-Presenting Cells ; immunology ; Antigens, CD ; Antigens, Differentiation ; immunology ; B7-1 Antigen ; immunology ; CD28 Antigens ; immunology ; CTLA-4 Antigen ; Humans ; Immunoconjugates ; Signal Transduction ; immunology ; T-Lymphocytes ; immunology

OBJECTIVETo study the protective role of Sertoli cell expressing FasL and CTLA-4Ig on allogeneic renal cell.

METHODSTesticular Sertoli cell and renal cell were prepared by digestion with enzymes. About 106 cells were injected into the subrenal capsule of allogeneic rats. 36 rats were divided into 3 groups: control group (10), co-transplantation group (16) and co-transplantation collaborated with CTLA-4Ig group (CTLA group, 10). Levels of serum IL-2 were tested on the 1st, 7th, 14th, 20th day after transplantation. The kidney was extracted on the 20th day. The survival of renal cells was determined by the Avidin Biotin Peroxidase Complex Technique (ABC); the brightness of grafts was measured by MD-20 image analysis system. Apoptosis within the grafts was observed with Terminal Deoxynucleotidyl Transferase-mediated X-dUTP Nick end Labeling (TUNEL) method.

RESULTSThe survival of renal cells in control group, co-transplantation group and CTLA group was 0, 14 and 10 respectively; The brightness values of co-transplantation group and CTLA group were 0.362 +/- 0.017 and 0.445 +/- 0.021, and the statistic differences between them were significant. Levels of serum IL-2 in CTLA group were lower compared with co-transplantation group, there being significant differences as well; Apoptosis of lymphocyte was observed within the grafts.

CONCLUSIONSSertoli cell and CTLA-4Ig have coordinative protective effect on allogeneic renal cell.

Abatacept ; Animals ; Antibodies ; Antigens, CD ; Antigens, Differentiation ; immunology ; CTLA-4 Antigen ; Immune Tolerance ; Immunoconjugates ; Kidney ; cytology ; Kidney Transplantation ; immunology ; Lymphokines ; Male ; Rats ; Rats, Wistar ; Sertoli Cells ; immunology

Idiopathic thrombocytopenia purpura (ITP) is an autoimmune disease which is characterized by destruction of platelets by macrophages in the reticuloendothelial system. Recent studies suggest that ITP is related to the abnormal activation and apoptosis of T/B cells which lead to failure of immune tolerance. Now it is becoming clear that costimulatory signals are required for full T/B cell activation and assumed to modulate T/B cells responses as well as other aspects of the immune system. This review focuses on the role and state-of-the-art advancements of costimulatory signals in ITP.
Antigens, CD ; immunology ; Antigens, Differentiation ; immunology ; Antigens, Differentiation, T-Lymphocyte ; immunology ; B-Lymphocytes ; immunology ; CD28 Antigens ; immunology ; CTLA-4 Antigen ; Humans ; Immune Tolerance ; Inducible T-Cell Co-Stimulator Protein ; Purpura, Thrombocytopenic, Idiopathic ; immunology ; Receptors, Tumor Necrosis Factor ; immunology ; Signal Transduction ; physiology ; T-Lymphocytes ; immunology ; physiology