Xenoislet rejection following pig-to-rat, pig-to-primate, and pig-to-man transplantation.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to A Karlsson-Parra.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Porcine fetal islet-like cell clusters (ICC) or isolated rat islets were implanted under the kidney capsule of normoglycemic rats. The animals were sacrificed 1, 3, 6, 12, or 24 days after transplantation, and a detailed morphological and phenotypic characterization of the different cellular subtypes infiltrating the xenograft was performed and compared with the rejection of allogeneic islets. In xenograft rejection a progressive infiltration of large, polygonal, macrophage-like cells, which with time became the dominating cellular subtype, occurred. These cells expressed the CD4 antigen and the macrophage-specific ED1 antigen. From day 6 and onward, a majority of the macrophage-like cells also expressed the CD8 antigen and the macrophage-specific differentiation antigen ED2. T lymphocytes, defined by their TCR alpha/beta or CD2 expression, were found in low numbers and mainly in the periphery of the graft. At the later stages of xenorejection a substantial number of eosinophilic granulocytes were also found. The allograft rejection, on the contrary, was characterized by a progressive infiltration of T lymphocytes, which with time became the dominating cellular subtype. No clear immunoglobulin or complement deposition was seen in the transplants before day 12, when IgG deposition was found in central necrotic areas of the xenograft. Previous experiments in rodents have underlined the crucial importance of CD4 positive cells in the xenograft rejection process. However, in none of these studies it was conclusively demonstrated that the CD4-expressing cells were T lymphocytes. The presence of CD4-expressing macrophages heavily infiltrating the porcine xenograft seen in our study may thus be in agreement with previous studies in which the anti-CD4 reactive cells were erroneously designated T lymphocytes. Interestingly, the findings in xenograft rejection in the present study have striking similarities with the defense mechanisms active against infections by large parasites such as helminths.
BACKGROUND: Normal and abnormal human parathyroid tissue express the T-lymphocyte protein CD4, and parathyroid and lymphocyte cells show similarities with respect to mechanisms of calcium permeability and regulation of the cytoplasmic calcium concentration. METHODS: Anti-Leu4, a monoclonal antibody recognizing the T-lymphocyte glycoprotein complex CD3, is used to immunohistochemically stain normal and abnormal human parathyroid cells and to explore influences on the parathyroid hormone (PTH) secretion of enzymatically dispersed parathyroid cells. RESULTS: Parathyroid glands of patients with different forms of hyperparathyroidism displayed variable expression of the anti-CD3 reactive complex. The stainings correlated both positively and inversely to immunoreactivity for a previously defined calcium sensor, the decreased expression of which may constitute a molecular basis for hyperparathyroidism. Incubation of parathyroid cells with the anti-Leu4 antibody inhibited PTH secretion and reduced its sensitivity to external calcium without influence on parathyroid cytoplasmic calcium concentration. CONCLUSIONS: The results suggest that the human parathyroid cells express a CD3-like molecule with the ability to interact in PTH release.
In recent years, interleukin-2 (IL-2) has been used as an immunomodulatory agent in the treatment of various malignant tumours. However, this treatment has been limited by serious side-effects, including toxic reactions in the lung. The effects of IL-2 treatment on inflammatory cell populations in the normal and irradiated rat lung were investigated in this study. IL-2 was continuously administered as a subcutaneous infusion over a 6 week study period. Irradiation was given in a single dose (25 Gy) the day after starting IL-2 treatment. Evaluation with bronchoalveolar lavage fluid (BALF) analysis and lung tissue morphology was made 6 weeks after irradiation. In nonirradiated rats, IL-2 treatment induced significant increases in the total number of inflammatory cells in the perivascular, interstitial and peribronchial tissues as well as in the alveolar space. These increases were not reflected in BALF; on the contrary, a significant decrease of the total numbers of inflammatory cells was found in BALF. Irradiation alone caused a more pronounced inflammatory response was significant increases of all inflammatory cells in all lung compartments, which was also reflected in BALF. Concomitant treatment with IL-2 and irradiation induced an enhanced accumulation of inflammatory cells in the perivascular and peribronchial tissues compared with irradiation alone. Thus, both irradiation and IL-2 treatment induce inflammatory reactions in the lung, but there were signs of synergistic effects seen in this study. Furthermore, the results also emphasize the difficulties in making sophisticated conclusions from BALF analyses alone.
Chloroquine can prevent photosensitivity reactions, but its mechanism of action is poorly understood. To investigate if the drug may interfere with inflammatory or immunological mechanisms of the UV-induced erythema of photosensitive patients, we studied the localization of chloroquine in the skin and its effect on the epidermal/dermal expression of IL-1, TNF-alpha, IL-6 and ICAM-1 and the occurrence of different lymphoid cells in normal skin and UVB-induced erythema in 8 patients with photosensitive discoid and systemic lupus erythematosus and 4 patients with polymorphic light eruption (PMLE), before and during chloroquine treatment. Using a specific monoclonal antibody against chloroquine, we found a strong granular staining pattern of mainly keratinocytes in all biopsy specimens from normal and erythematous skin during chloroquine treatment. In non-irradiated skin, T lymphocytes, macrophages and HLA-DR expressing cells were sparsely distributed within the dermis in similar amounts before and during chloroquine treatment. In UVB-induced erythema an increase in the number of these cells, mainly located in the dermal perivascular area, was seen before medication. During chloroquine treatment such cellular infiltration was reduced. ICAM-1 expression was detected on the endothelium of dermal vessels but not on keratinocytes. The accumulation of chloroquine in the epidermis and the decreased cellular infiltration in erythematous skin during chloroquine treatment indicate a local anti-inflammatory effect. This effect may be due to either unspecific UV-protective properties of the drug or to some specific downregulating action by chloroquine on keratinocyte function.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
A mouse-to-rat heart retransplantation model was used to study the effects of complement depletion and antibody production with regard to graft survival and anti-donor antibody specificity. Retransplantation was performed 3 weeks after the first transplantation in the presence of absence of 15-deoxyspergualin (DSG) immunosuppression. Untreated animals rejected their first graft after 3 days and retransplantation resulted in a hyperacute rejection within 2 min. A low titer of preformed anti-mouse lymphocytotoxic antibodies of the IgM subclass was found in serum collected from the unoperated rat. The rejection gave rise to a synthesis of IgG antidonor antibodies reacting with both graft endothelium and sarcolemma. Immunofluorescent staining of the rejected first heart graft showed moderate IgM and IgG antibody deposits on the graft vascular endothelium, while only IgG was found in the second graft. There was no C3 deposition found in the first mouse graft, as was the case in the second mouse graft. Anti-mouse antibodies cross-reacted with hamster antigens and a hyperacute rejection of a hamster heart graft occurred in a mouse-sensitized rat. Immunofluorescent staining revealed that the antibodies did not bind to hamster heart endothelium, as was expected, but, instead, to graft sarcolemma. DSG treatment prolonged the survival of the first graft by a median of 8 days. Continuous treatment until retransplantation resulted in a prolongation to 30 (20-127) min of the survival of the second graft and no increase in antibody titers against mouse antigens was observed. However, immunofluorescent staining revealed a weak binding of anti-mouse antibodies of the IgM subclass in the rejected mouse heart graft. Additional complement depletion with cobra venom factor in DSG-treated animals resulted in a prolongation of the median graft survival to 48 hr (6-96). No sign or minimal signs of antibody deposition were found in these grafts, but histology revealed massive mononuclear infiltration. In conclusion, xenograft transplantation in a concordant situation results in a shift of antidonor antibody Ig synthesis from IgM to IgG. If daily DSG treatment is administered from the day of transplantation, this reduces the synthesis of antidonor antibodies, and if complement is also depleted, the survival of the second graft is prolonged. The significance of the mononuclear infiltration remains to be established.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
OBJECTIVE: To reconstitute a dysfunctional form of complement factor C3 in a patient with a systemic lupus erythematosus (SLE)-like syndrome. METHODS: The propositus was treated with plasma infusions during five sessions over a period of eight months. RESULTS: The alternative pathway was reconstituted to normal levels for approximately two to three days after each infusion. C3 fragments were incorporated into previously detected deposits of IgG and IgM at the dermal-epidermal junction and the immune complex levels gradually decreased during the whole treatment period. CONCLUSION: The reconstitution appears to result in the solubilisation of tissue immune complexes and a subsequent transportation to the fixed macrophage system.
Explore the source record for details and available documents.
OBJECTIVE: To elucidate the possible development of Sjögren's syndrome in young women with previous postpartum thyroiditis, a clinical and laboratory case-control followup study was undertaken. METHODS: Forty female patients (mean age 36 years) with well documented postpartum thyroiditis 5 years previously and 30 healthy mothers (mean age 36 years) who all had undergone normal partus an average of 5 years previously, were included in the study. RESULTS: Symptoms of dry eyes, caries, arthralgias, swollen joints and fatigue were reported significantly more often in women with previous postpartum thyroiditis compared with healthy mothers of the same age (p < 0.05). Using an ELISA with purified (SSA)Ro and (SSB)La proteins derived from a human cell line as antigens, 34% of the women were anti-SSB positive and 46% were anti-SSA positive at followup. Furthermore, 15/35 women with a history of postpartum thyroiditis (43%) had objectively impaired tear and/or saliva production; 5 of 24 investigated women had keratoconjunctivitis sicca (KCS) and 2 of 7 salivary gland biopsies showed chronic lymphocytic sialadenitis. Three women (8.6%) had the combination of KCS and xerostomia. CONCLUSION: Laboratory and clinical features of Sjögren's syndrome are frequently seen in younger women with previous postpartum thyroiditis.
The distribution of T- and B-lymphocytes, HLA-DR-expressing cells, and macrophages was determined using monoclonal antibodies in frozen biopsy sections of nasal polyps from 12 patients, and of nasal mucosa from five disease-free controls. The relative proportion and spatial distribution of different lymphoid cells was similar with regards to both nasal polyps and normal mucosa. Numerous scattered T lymphocytes (Leu4-positive) and HLA-DR-expressing macrophage/dendritic-like cells were shown and tended to accumulate in the subepithelial areas. Aggregates of T lymphocytes and HLA-DR-positive cells were also found close to deeper glands. In the submucosal clusters, the Leu3a-positive ("helper/inducer") cells were more common than the Leu2a-positive ("suppressor/cytotoxic") cells. Furthermore, a number of epithelial, non-lymphoid cells were found to express the HLA-DR antigen, which suggests an active role for the epithelium in the immunological response of the normal mucosa as well as that of the nasal polyp.
Explore the source record for details and available documents.
OBJECTIVE: We studied the incidence, severity, histopathologic features, and status of infection in a spontaneous polyarthritis which occurs in male DBA/1 mice. METHODS: Over a 25-week period, the arthritis was evaluated macroscopically in naive mice of different strains. The histopathology was evaluated at different phases of the disease. Virologic and bacteriologic investigations were performed. RESULTS: The arthritis occurs in approximately 80% of aging male DBA/1 mice. The disease is chronic and destructive, and the affected joints are characterized by synovial lining proliferation and infiltration of inflammatory cells, mainly mononuclear. The susceptibility appears to be dependent on both sex-linked and non-sex-linked genes, since female DBA/1 mice are not affected and since male BALB/c housed in the same colony are only marginally affected. CONCLUSION: This first description of a spontaneous arthritis in aging male DBA/1 mice should provide new opportunities to study general features of a chronic and intermittent arthritis in a well-characterized strain, in which no generalized aberrations of the immune system have been described.