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M de Sousa

Publications and source records attributed to M de Sousa.

At least 73 records · Page 4Linked to original sources
PubMed1985

Regulatory influence of thymopentin on splenic T cell sets of thymectomized and aged mice.

Thymectomy of mice aged 6-8 weeks causes a disproportion of splenic T cell sets, the Ly123 set being relatively decreased and the Ly23 set relatively increased (Ly123 decrease: Ly23 increase). A similar disproportion of splenic T cell sets was found to occur spontaneously with advancing age (12-18 months). By PA-SRBC assay, the total number of splenic Lyt+ cells is not appreciably reduced by thymectomy or by aging, but the Thy-1+ cell count falls by about 40% according to both PA-SRBC and cytotoxicity assays. Thus there is an increase in the number of Lyt+ cells expressing sub-threshold amounts of Thy-1. The following observations show that thymopentin (TP-5), a synthetic pentapeptide analogue of thymopoietin, counteracts these changes in thymectomized and aged mice. As reported previously, the capacity of C3H/HeJ female mice to reject C3H/HeJ male skin was raised by thymectomy, or with age, and treatment with TP-5 substantially normalized the rejection response. Here we correlate these findings with changes in the profile of splenic T cell sets. The splenic T cell set profile of thymectomized B6-Tlaa male and female mice was essentially restored by TP-5. The Ly123 decrease: Ly123 increase change caused by thymectomy was not associated with obviously altered proportions of Qa-1+ and Qa-1- subsets. Treatment of aged mice with TP-5 also prevented the onset of changes in splenic T cell sets that occur spontaneously with age. Thus thymectomy and aging give rise to disproportions of splenic T cell sets, and in C3H female mice to a heightened capacity for male skin rejection, both effects being largely abrogated by the TP-5 derivative of thymopoietin.

Aging↗
PubMed1985

Disproportionate lymphoid cell subsets in thalassaemia major: the relative contributions of transfusion and splenectomy.

The relative proportions of T-cell (OKT3-positive, OKT4-positive and OKT8-positive) and B-cell (SIg-positive) populations in peripheral blood obtained from 29 chronically transfused patients with beta-thalassaemia major were compared with those of 17 healthy controls. Changes attributable to blood transfusion and/or splenectomy are described. The percentage of OKT8-positive (T-suppressor) cells found in the thalassaemic patients increased linearly (P less than 0.001) with the number of units transfused, irrespective of splenectomy. The percentage of OKT4-positive (T-helper) cells varied inversely with increasing transfusion in nonsplenectomized patients while in those who were splenectomized no significant correlation was apparent. Thus, in both groups of patients the T4/T8 ratio declined in a transfusion-related manner. The splenectomized patients experienced a marked and persistent lymphocytosis due to an increase in the number of both T- and B-cells. When the results were expressed as percentages, the greatest increase occurred in the number of B-cells, this increase being unrelated to the number of transfusions received. None of the serum parameters usually associated with iron overload or abnormal liver function correlated with the observed increases in T-suppressor and SIg-positive cells. These findings corroborate reports that transfusion of blood products may lead to decreased T4/T8 ratios. However, none of the patients studied manifested clinical signs of acquired immune deficiency syndrome (AIDS). Accordingly, studies which define transfusion related AIDS on the basis of analyses with monoclonal antibodies must be viewed with caution.

Adolescent↗
PubMed1985

Ferritin in neuroblastoma. Impact of tumor load and blood transfusions.

Serial serum ferritin (SF) levels were measured in 36 patients with neuroblastoma seen at Memorial Sloan-Kettering Cancer Center (MSKCC) between January 1981 and December 1982. The significance of the associations among SF, stage and extent of disease, number of blood transfusions, liver function, serum iron (Fe), total iron-binding capacity (TIBC), and transferrin saturation was investigated. Although a dominant statistical correlation was found between SF and number of blood transfusions, the results suggest that amount of disease contributes to increasing SF levels. Serum ferritin levels increased on average in a linear fashion with number of blood transfusions in patients free of disease or with minimal disease. In patients with bulky disease, this increase was exponential (p value less than 0.01). Application of a reverse hemolytic plaque assay to the analysis of ferritin secretion by cells demonstrates that tumor cells do secrete ferritin in vitro.

Adolescent↗
PubMed1984

Differential effect of two monoclonal anti-Lyt-1 alloantibodies on lymphocyte distribution in vivo.

The effect of anti-Lyt-1 monoclonal antibody treatment on the in vivo migration properties of mouse T lymphocytes was examined. Cells were treated with antibody in the presence or absence of complement. T cells of the Lyt-2 cytotoxic/suppressor phenotype were selected from B6 spleen cell suspensions by cytotoxic elimination with an allospecific anti-Lyt-1.2 antibody. These cells were labelled with 51Cr and transferred to syngeneic recipients which were killed 1 or 24 hr later for assessment of radiolabel tissue distribution. In vivo migration of anti-Lyt-1.2 selected cells was similar to that of unselected T cells. By contrast, a functionally and phenotypically identical population selected from C3H spleen T cells with an anti-Lyt-1.1 monoclonal antibody showed increased accumulation in recipient liver and a decline in recovery from lymph nodes and spleen. Treatment with anti-Lyt-1.1 in the absence of complement caused even greater localization to the liver, with a simultaneous poor recovery from lymphoid tissues, similar treatment of cells from B6 Lyt-1.1. congenic mice also resulted in altered migration. Treatment of B6 lymphocytes with anti-Lyt-1.2 in the absence of complement caused little change in the normal T cell tissue localization. These results suggest that selected Lyt-2 cells, reported to express low levels of Lyt-1 antigen undetectable by conventional u.v light microscopy immunofluorescence and serological methods, may contain residual bound antibody which can result in opsonization and sequestration of the cells by recipient stromal cells after in vivo transfer. Binding of the antibody directed to the Lyt-1.2 allospecificity of B6, although of the same immunoglobulin class and selecting for a similar functional set by cytotoxic elimination, does not cause such sequestration in vivo.

Animals↗
PubMed1984

Lyt phenotype, lymphocyte migration and the selective tissue positioning of mouse T cell sets.

Functionally defined mouse Lyt-1 and Lyt-2 cell sets were selected from peripheral lymph nodes by cytotoxic elimination with anti-Lyt monoclonal antibodies. The selected populations were labelled with 51Cr or [3H]-adenosine and traced in syngeneic recipients at 1, 24, 45 and 65 hr after intravenous injection. Recovered radioactivity in recipient organs was measured by gamma-counting. The exact tissue positioning of the labelled cells was determined by autoradiography and labelled cell counting in spleen, lymph node and Peyer's patch microenvironments. Selected cell sets differed from unselected T cells in two ways: (i) Selected Lyt-1 and Lyt-2 cells showed some decline in recovery from recipient lymph nodes at 24 hr after injection; (ii) Lyt-2 cells showed enhanced localization to Peyer's patches. Autoradiographic analysis of microenvironmental tissue positioning of [3H]-adenosine labelled cells confirmed a relatively higher localization of Lyt-2 cells in Peyer's patches than in lymph nodes. In both tissues, the majority of the labelled cells were found in T areas. In the spleen, a higher proportion of Lyt-2 cells was seen in T-independent follicular areas.

Animals↗
PubMed1983

Thymus cell differentiation and in vivo T-cell migration. I. Migration of lectin-selected thymocytes.

The in vivo quantitative distribution and tissue positioning of mouse thymocytes selected in vitro by Lyt phenotype and lectin binding properties were examined. Lyt 1+2- thymocytes were selected for by cytotoxic elimination; peanut agglutinin (PNA) and soybean agglutinin (SBA) binding and nonbinding thymocyte fractions were separated by an agglutinin technique. Selected cell suspensions were labelled in vitro with 51chromium (51Cr) or [3H]adenosine. Labeled washed cells were injected intravenously into syngeneic recipients which were killed at 1, 24 or 48 hr. In recipients of 51Cr-labeled cells, tissues were collected for gamma counting, and the overall percentage recovery of injected radiolabel from the various tissues was assessed. Tissues collected from recipients of [3H]adenosine-labeled cells were fixed, sectioned, and processed for autoradiography; the positioning of labeled cells within the tissues was determined. Selected Lyt 1+2-, PNA-, and SBA- sets all showed significantly enhanced entry into lymph nodes and intestinal lymphoid tissues. Entry of SBA+ cells into these tissues was comparable to that of peripheral T cells. PNA- and SBA- selected sets, but not Lyt 1+2- selected cells, also showed increased localization to the spleen and lungs, and decreased localization to the liver. By autoradiography, PNA- cells entered lymphoid tissues much more than PNA+ cells, and at 1 hr fewer PNA+ cells in spleen were associated with lymphoid follicles. At 24 and 48 hr almost all labeled cells in lymphoid tissues were positioned in T-dependent areas. These results suggest that enrichment for thymocyte subpopulations described as "mature" also enriches for cells with the ability to enter lymphoid tissue. They also suggest that interactions at other tissue sites are important in the determination of in vivo migration, and that surface carbohydrate composition is an important factor in this determination.

Animals↗
PubMed1983

Ferritin secretion by human mononuclear cells: association with HLA phenotype.

A number of different observations indicate that cells of the immune system can participate in the prevention of potential tissue toxicity from iron accumulation and that, in turn, iron and iron binding proteins have important effects on immune responses. The current studies were undertaken to examine a specific aspect of the interaction of iron with human peripheral blood mononuclear cells. A modified hemolytic plaque-forming assay was used to measure ferritin secretion in vitro by phytohemagglutinin activated or nonactivated mononuclear cells in response to stimulation by ferric citrate. Cells from 55 unrelated healthy subjects collectively representing all well-defined HLA-A, B, C, and DR antigens were studied. There were large reproducible differences in the numbers of plaques formed by different individuals, and there was a statistically significant increase in the frequency of the HLA determinant A3 among the "low" responders. Ferritin secretion measured with an antibody specific for acidic ferritin also showed a distinction between A3 and non-A3 donors. In preliminary cell mixing studies, ferritin secretion by mononuclear cells was shown to require the presence of monocytes and to be influenced by the secretion characteristics of both the monocyte and the T-cell donor. These results may provide a clue to the mechanism of development of idiopathic hemochromatosis which is an HLA-A-linked autosomal recessive disease associated with the specific HLA antigen HLA-A3.

Cell Adhesion↗
PubMed1983

Relative subunit composition of the ferritin synthesized by selected human lymphomyeloid cell populations.

Biosynthesis of ferritin subunits by cell sets isolated from normal human peripheral blood, spleens of Hodgkin's disease patients, and tumor cell lines were investigated. Normal mature hematopoietic cells made a ferritin with more H (21K) than L (19K) subunits. The reverse was found for a promyelocytic tumor cell line and tumor cell lines derived from other tissues. Two dimensional electrophoresis indicated H has a lower pI than L. Therefore relative proportions of the two subunits contribute to the electrophoretically distinct forms of the isoferritins. In response to increasing concentrations of iron in vitro, a selected monocyte population synthesized more H than L; L biosynthesis however increased more than H. Some possible regulatory implications of these observations are discussed.

Cell Line↗
PubMed1982

Spleen lymphocyte populations in patients with Hodgkin's disease--properties of cells with different densities.

Spleen lymphocytes from five patients with Hodgkin's disease (HD) type mixed cellularity and five normal controls were studied. An increased percentage of 'null cells' was observed in three out of the five patients studied. The two other patients had increased percentage of T lymphocytes. Lymphocytes from spleen with HD had a decreased ability to respond to suboptimal concentrations of T cell mitogens. When these cells were fractionated in a discontinuous density gradient a subpopulation of cells, unable to respond to Con A, was recovered from the dense cell fractions. The implications of the present findings to the understanding of the physiopathological changes in HD are discussed.

Adolescent↗
PubMed1981

Identification of leukemia-associated inhibitory activity as acidic isoferritins. A regulatory role for acidic isoferritins in the production of granulocytes and macrophages.

Acidic isoferritins have been identified as leukemia-associated inhibitory activity (LIA), which suppresses colony and cluster formation of colony-forming unit-granulocyte macrophages from normal donors but not from patients with leukemia. LIA was detected in all ferritin preparations tested, including ferritin isolated from normal heart, spleen, liver, and placental tissues, and from the spleens of patients with chronic myelogenous leukemia and Hodgkin's disease. Purified preparations of LIA were composed almost entirely of acidic isoferritins, as determined by immunoassay, radioimmunoassay, and isoelectric focusing. The inhibitory activity in the LIA and ferritin samples was inactivated by a battery of antisera specific for ferritin, including those prepared against acidic isoferritins from normal heart and spleen tissues from patients with Hodgkin's disease, and those previously absorbed with basic isoferritins. Antisera absorbed with acidic isoferritins did not inactivate the inhibitory activity. Separation of LIA and chronic myelogenous leukemia and normal spleen ferritin by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and isoelectric focusing confirmed that the regions of peak inhibitory activity corresponded in each to an apparent molecular weight of approximately 550,000 and to a pI value of 4.7. Similar physicochemical characteristics included inactivation by methods that dissociate ferritin molecules into subunits and by treatment with trypsin, chymotrypsin, pronase, and periodate. The purified preparations were extremely stable to heat treatment. The glycoprotein nature of the inhibitory activity was substantiated because it bound to concanavalin A-Sepharose and was eluted off by alpha-methyl mannose. Inhibitory activity of the activity of the acidic isoferritins was detected at concentrations as low as 10(-17)-10(-19) M and iron saturation did not appear to be necessary for its action. These results implicate acidic isoferritins in the regulation of normal myelopoiesis and suggest a role for them in the progression of leukemia.

Bone Marrow↗
PubMed1981

Differential inhibition of the MLR by iron: association with HLA phenotype.

The effect of iron on the MLR was examined by pretreating peripheral blood mononuclear cells from 77 unrelated Caucasians with five concentrations of Ferric-citrate (10.0 mM, 1.0 mM, 0.1 mM, 0.01 mM and 0.005 mM). After incubation with the metal, the cells were washed and cultured in a one-way MLR with a pool of stimulator cells. Cell viability remained unchanged (greater than 90 percent) during the 6-day culture period. Citrate per se had no effect on either the responder or the stimulator population. Iron treatment influenced the MLR in the following ways: (1) a variable degree of inhibition was observed which related to the dose of Ferric-citrate used and to HLA phenotype, (2) the responder but not the stimulator cells were affected, (3) no statistically significant differences were seen between female and male donor cells and (4) the mean percent response of cells from HLA-A2 donors were significantly (0.005 less than P less than 0.01) less susceptible to iron exposure than those from non-HLA-A2 individuals. The present results indicate that iron can interact with lymphoid cells and influence some immunological functions in vitro. The possibility is discussed that similar interactions take place in vivo which could contribute to the prognosis of certain diseases associated with particular HLA phenotypes.

Adult↗
PubMed1981

Impaired T-cell mitogen responses in some patients with thalassemia intermedia.

Ten thalassemia intermedia patients were tested for their mitogenic responses to phytohemagglutinin P (PHA), concanavalin A (Con A) and pokeweed mitogen (PWM). Impaired responses to PHA and Con A were observed in patients with serum-iron levels higher than 200 microgram/dl. Responses within or slightly higher than those in the normal range were observed in patients with serum-iron lower than 200 microgram/dl. By contrast, no significant changes occurred in the majority of the responses to PWM.

Adolescent↗
PubMed1981

Sex-related differences in tumor progression associated with altered lymphocyte circulation.

Male and female ACI rats were inoculated with the syngeneic H-4-II-E hepatoma, and the natural history of the tumor, histopathology, and lymphocyte migration were studied. The tumor formed a.s.c. mass in all 16 males and in 22 of the 26 females given injections. In the males, tumors progressed, and all animals died with the mean survival time of 54 days. Complete tumor regression was observed in all but two females. In the females, there was prominent lymphocytic infiltration of the tumor, while males had no cellular reaction at the tumor site. The regional lymph nodes in males usually contained metastases and were nonreactive. The female lymph nodes did not contain metastases but contained many lymphocytes within the peripheral sinus and sinusoids. Six male-female pairs were castrated before tumor inoculation. Castration had no effect on the natural history or the etiology of the tumor. Comparing seven normal control male-female littermate pairs, there were no differences in lymphocyte accumulation in the lymph nodes 22 hr following injection of 51Cr-labeled syngeneic lymphocytes. In seven tumor-bearing male-female littermate pairs, there was a significant decrease in lymphocyte migration to the lymph nodes (p less than 0.001) in tumor-bearing males as compared to that in both their female littermates and control males. Depressed lymphocyte circulation in the males was associated with rapid progression of tumors resulting in the death of the animals. Unimpaired lymphocyte mobilization in the tumor-bearing females was associated with complete regression in most animals.

Animals↗
PubMed1980

Ferritin synthesis by human T lymphocytes.

Mononuclear cells from peripheral blood of normal humans, unselected spleen cells from patients with Hodgkin's disease, and selected T and non-T lymphoid cells from normal peripheral blood and from the spleens of Hodgkin's disease patients were examined for de novo synthesis and secretion of ferritin. After precipitation of labeled lysates and supernatants from unseparated and selected T cells with antiserum to human liver ferritin, two bands were visible on sodium dodecyl sulfate-polyacrylimide gel analysis. The two bands were detected in molecular weight regions 19,000 and 21,000, which are thought to represent the L and H subunits of the ferritin molecule, respectively. The slower band (subunit H) was more radioactive than the faster band (subunit L). The H subunit is found in greater amounts in the serum of some tumor patients, but its cellular origin has not been established. The present findings indicate that cells of the immune system contribute to the synthesis and secretion of a ferritin molecule with a high proportion of H subunits.

Cell Separation↗