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Biomedical subjects

S Strober

Publications and source records attributed to S Strober.

At least 199 records · Page 11Linked to original sources
PubMed1977

Induction of specific tissue transplantation tolerance using fractionated total lymphoid irradiation in adult mice: long-term survival of allogeneic bone marrow and skin grafts.

BALB/c mice were treated with fractionated high dose (3,400 rads) total lymphoid irradiation (TLI), and given semiallogeneic (BALB/c x C57BL/Ka) or allogeneic (C57BL/Ka) bone marrow and/or skin allografts. TLI alone prolonged the mean survival time (m.s.t.) of C57BL/Ka skin grafts to 49.1 days (control, 10.7 days). Shielding of the thymus during TLI produced only a slight increase in graft survival (m.s.t., 19 days). TLI combined with splenectomy was no more effective than TLI alone. Infusion of 10(7) semiallogeneic or allogeneic bone marrow cells after TLI produced stable chimeras in 7/8 and 8/15 recipients, respectively. Chimeras were specifically tolerant to donor tissues, since C57BL/Ka skin grafts were accepted for more than 250 days, but third-party (C3H/He) skin grafts were rejected rapidly. In addition, chimeric lymphocytes responded to C3H/He and C3H. Q but not to C57BL/Ka cells in the one-way mixed leukocyte reactions. BALB/c C57BL/Ka chimeras showed no clinical evidence of graft vs. host disease. These findings may have application of clinical organ transplantation, since (a) the recipient treatment (TLI) has already been shown to be safe in humans, (b) donors and recipients can be completely allogeneic, and (c) bone marrow and skin graft survival was permanent (greater than 250 days).

Animals↗
PubMed1977

The relationship between surface immunoglobulin isotype and immune function of murine B lymphocytes. I. Surface immunoglobulin isotypes on primed B cells in the spleen.

We investigated the ability of IgM-, IgD-, and IgG-bearing cells from the spleens of (BALB/c x C57BL/Ka)F1 mice primed to dinitrophenyl-bovine serum albumin (DNP-BSA) to restore the adoptive secondary anti-BSA and anti-DNP antibody responses. A rabbit anti-mouse IgD antiserum was prepared and the specificity documented by radioimmunoprecipitation, and cell surface staining. Purified populations of IgM-, IgD-, and IgG-bearing cells were prepared by immunofluorescent staining with isotype-specific reagents, and sorting on the fluorescence activated cell sorter. Bright or dull cells were transferred to irradiated syngeneic recipients which were challenged with DNP-BSA in saline. Unfractionated spleen cells restored an adoptive secondary serum antibody response which was all IgG (2-mercaptoethanol resistant). Purified IgM- or IgD-bearing cells restored both the secondary IgM and IgG antibody response. IgG-bearing cells restored only the IgG response. In addition, the IgG-bearing cells appear to suppress the adoptive secondary IgM response, since depletion of IgG-bearing cells from transferred spleen cells results in a marked increase in the adoptive IgM response.

Animals↗
PubMed1977

The relationship between surface immunoglobulin isotype and immune function of murine B lymphocytes II. Surface immunoglobulin isotopes on unprimed B cells in the spleen.

We investigated the ability of IgM-, IgD-, and IgG-bearing cells from the spleens of unprimed (BALB/c x C57BL/Ka)F1 mice to restore the adoptive primary anti-BSA and anti-DNP antibody responses. Purified populations of isotype-specific cells were prepared by immunofluorescent staining and sorting on the fluorescence activated cell sorter. Bright or dull cells were transferred to irradiated syngeneic recipients which were challenged with DNP-BSA in complete Freund's adjuvant. Unfractionated spleen cells as well as IgM- and IgD-bearing cells restored the adoptive primary IgM and IgG antibody response. IgG-bearing cells restored a vigorous adoptive response which was all IgG (2-mercaptoethanol resistant). Depletion of IgG-bearing cells markedly increased the adoptive IgM response, and depletion of IgM-bearing cells markedly increased the IgG response. However, depletion of IgD-bearing cells resulted in a considerable reduction in the IgG response. The latter finding indicates that there is a subpopulation of IgD-bearing cells which express little or no surface IgM and which make a considerable contribution to the adoptive primary IgG response.

Animals↗
PubMed1977

The long term effects of radiation of T and B lymphocytes in the peripheral blood after regional irradiation.

The long term alterations of T and B lymphocytes in the peripheral blood of patients treated with regional irradiation for various malignancies were examined. Eighty patients were tested at various intervals after the completion of irradiation. Absolute lymphocyte counts, the percentages of T cells and B cells, and the blastogenic response to phocyte reaction (MLR) were determined. Nearly all patients initially had absolute lymphocytopenia and one-third of the patients tested 3 years after completion of irradiation had lymphocyte counts which were more than two standard deviations below the normal range. The depression was not specific for either the T-or B-lymphocyte subpopulations. The PHA response was impaired for extended periods of time after the completion or irradiation. Differences in the mean response of lymphocytes to PHA were noted for all concentrations of the mitogen, but were most marked with suboptimal concentrations of PHA. The MLR was below the lower limits of normal in 70% of the recently irradiated patients. There was a gradual recovery of the ability to respond in the MLR, and all patients tested more than 4.5 years after the completion of therapy had a normal response. These results were compared with those obtained in patients treated with total lymphoid irradiation for Hodgkin's disease. Although three appeared to be a difference in the effect of radiation on lymphocyte subpopulations in the two groups, the effects on lymphocyte function were similar.

B-Lymphocytes↗
PubMed1977

T- and B-cells in immunologic diseases.

Three major subpopulations of lymphocytes have been identified in human peripheral blood: thymus-derived (T) lymphocytes, bursa-equivalent (B) lymphocytes, and null (neither T nor B) lymphocytes. T-lymphocytes are commonly identified by a surface receptor for sheep erythrocytes, and by heterologous antisera raised against human thymus cells and absorbed with human B-cell leukemias or lymphoblastoid cell lines. B-lymphocytes are routinely enumerated by immunofluorescent staining technics for surface immunoglobulin, or by assays for the receptor for C3. Null cells bear a receptor for the Fc portion of immunoglobulin, and are killer (K) cells in antibody-dependent cellular cytotoxicity. Accurate quantitation of T- and B-cells in disease states has been hampered by marked contamination of monocytes in populations of peripheral blood lymphocytes purified by density gradients, binding of autologous immunoglobulin to the surface of non-B cells, and disease-associated alterations of T- and B-cell surface markers. Assays for peripheral blood T- and B-cells may be of significant clinical value in the early diagnosis of lymphocytosis of unknown origin, congenital immunodeficiency disorders, organ transplant rejection crises, and Hodgkin's disease.

Animals↗
PubMed1976

Interaction between serum factors and T lymphocytes in Hodgkin's disease. Use as a diagnostic test.

We studied the mechanism of defective binding of sheep erythrocytes to the surface of peripheral blood T lymphocytes (E-rosette-formation) in Hodgkin's disease. The decreased percentage of E-rosette-forming cells (range, 21 to 77 per cent) in 25 patients with Hodgkin's disease was reversed and returned to normal range (52 to 78 per cent) by prior incubation of the T lymphocytes in tissue-culture medium with 20 per cent fetal-calf serum for 18 to 24 hours. The percentage of E-rosette-forming cells was suppressed by additional incubation with serum from patients with Hodgkin's disease (range, 20 to 61 per cent) but not with serum from patients with other neoplasms or from normal subjects (range, 52 to 74 per cent). Only target T lymphocytes from patients with Hodgkin's disease were suppressed by Hodgkin-disease serum. The findings suggest that there is a specific interaction between serum factors and the surface of peripheral blood T lymphocytes in Hodgkin's disease.

Female↗
PubMed1976

Long-term survival of skin allografts in mice treated with fractionated total lymphoid irradiation.

Treatment of recipient Balb/c mice with fractionated, high-dose total lymphoid irradiation, a procedure commonly used in the therapy of human malignant lymphomas, resulted in fivefold prolongation of the survival of C57BL/Ka skin allografts despite major histocompatibility differences between the strains (H-2d and H-2b, respectively). Infusion of 10(7) (C57BL/Ka x Balb/c)F1 bone marrow cells after total lymphoid irradiation further prolonged C57BL/Ka skin graft survival to more than 120 days. Total lymphoid irradiation may eventually prove useful in clinical organ transplantation.

Animals↗
PubMed1976

Alterations in T and B lymphocytes in heart transplant patients early and late postoperatively.

Alterations in the percent and absolute number of thymus-derived (T) and bursa-equivalent (B) lymphocytes in peripheral blood were followed in 10 patients treated with antithymocyte globulin, prednisone, and azathioprine after cardiac transplantation. During the 1st postoperative wk the percent of T cells dropped below 10% in almost all cases (normal range, 65-91%) with a concomitant rise in the percent of B cells. However, the absolute T- and B-cell counts were both markedly depressed (less than 200 cells/mm3). During the 7-wk postoperative period the percent of T cells rose to 45-60% and the absolute count rose from 100 to 350 cells/mm3 (normal range, 1,092-2,400 cells/mm3). Although the percent of B cells was elevated (35-50%) during this period, the absolute B-cell count remained below the range of normals (268-640 cells/mm3). Follow-up of long-term survivors (3-60 mo postoperative) showed a continued marked T (467 cells/mm3) and B (95 cells/mm3) lymphocytopenia. Chronological relationships between the percent and absolute T-cell count and episodes of graft rejection in individual patients are discussed as possible adjuncts in the prediction of rejection crises.

Adolescent↗
PubMed1976

Long term effects of radiation of T and B lymphocytes in peripheral blood of patients with Hodgkin's disease.

Total lymphocyte counts, and the percentage of T and B lymphocytes and monocytes in untreated patients with Hodgkin's disease were not significantly different from those observed in normal donors. At the completion of radiotherapy, the mean total lymphocyte count of 503/mm3 was 4 SD below the mean for normal controls. Although a group of 26 patients in continuous complete remission from 12 to 111 mo after radiation treatment regained normal total numbers of lymphocytes and monocytes, they exhibited a striking T lymphocytopenia and B lymphocytosis. Concomitantly, there was a significant increase of null (neither T nor B) lymphocytes. The response of peripheral blood lymphocytes to phytohemagglutinin, concanavalin A, and tetanus toxoid before treatment was significantly impaired. 1-10 yr after completion of treatment there seemed to be little or no recovery of these responses. The capacity of peripheral blood lymphocytes to respond to allo-antigens on foreign lymphocytes in vitro (mixed lymphocyte reaction) was normal in nine untreated patients. However, the mixed lymphocyte reaction was markedly impaired during the first 2 yr after treatment. There was a partial and progressive restoration of the mixed lymphocyte reaction during the next 3 yr, and normal responses were observed in patients in continuous complete remission for 5 yr or more. The in vivo response to dinitrochlorobenzene was also examined. 88% (15/17) of patients initially sensitive to dinitrochlorobenzene were anergic to the allergen at the completion of a course of radiotherapy, but nine of these regained their hypersensitivity response during the 1st yr after treatment. This data suggests that there is a sustained alteration in both the number and function of circulating T cells after radiation therapy in patients with Hodgkin's disease which may persist for as long as 10 yr after treatment. The restoration of cell mediated immune functions after radiotherapy is time dependent and its kinetics may differ for various T-cell functions. The implications of these findings with respect to the state of immunological competence after radiotherapy are discussed.

B-Lymphocytes↗
PubMed1976

Maturation of b lymphocytes in rates. III. Two subpopulations of memory B cells in the thoracic duct lymph differ by size, turnover rate, and surface immunoglobulin.

We examined the ability of large and small thoracic duct cells obtained from Lewis rats primed to DNP to restore the adoptive secondary anti-DNP response in irradiated syngeneic hosts given an excess of T helper cells. The large cells were four to five times more active on a per cell basis than were the small cells. However, the large cells constitute only 7 to 8% of the thoracic duct cells and, therefore, make a minor contribution to the restorative activity of the unfractionated cells. Pretreatment of thoracic duct cell donors with high specific activity 3H-TdR for 48 hr before cannulation markedly reduced the memory B cell activity of the large cells, but had little effect on that of small cells. In addition, the activity of the large cells diminished with time after primary immunization, but that of the small cells remained stable. Immunofluorescent staining of the large and small cells for surface IgM and IgG, and subsequent sorting on the fluorescence-activated cell sorter (FA CS), showed that surface IgM was present on large memory B cells, and that IgG was present on small memory B cells. The experimental results suggest that two subpopulations of memory B cells in the thoracic duct lymph differ by size, rate of turnover, persistence after primary immunization, and class of surface IgG.

Animals↗
PubMed1976

Reversal of cell surface abnormalities of T lymphocytes in hodgkin's disease after in vitro incubation in fetal sera.

The capacity of periphal blood lymphocytes from patients with untreated Hodgkin's disease to form E rosettes with sheep erythrocytes and to respond in vitro to PHA stimulation were found to be profoundly impaired. In 49% of the patients, the percentage of E rosette-forming cells (E-RFC) was more than two standard deviations below the mean for normal donors. Overnight incubation of the peripheral blood lymhocytes from these patients in culture media containing 20% fetal calf serum was followed by restoration of the percentage of E-RFC up to normal levels. Similar results have been observed after incubation in fetal human serum, but not in adult human AB serum or adult bovine serum. Incubation of peripheral blood lymphocytes from untreated patients in20% fetal calf serum also resulted in a remarkable restoration of their capacity to respond normally to PHA. Possible mechanisms involved in these reversible cell surface and in vitro lymphocyte function abnormalities in Hodgkin's disease are discussed.

Cell Membrane↗
PubMed1975

Quantitation of T and B lymphocytes and cellular immune function in Hodgkin's disease.

Peripheral blood T and B lymphocytes were quantitated in 42 patients with untreated Hodgkin's disease and the results compared with the response to phytohemagglutinin (PHA) stimulation and delayed hypersensitivity skin testing. T lymphocytes were identified by an in vitro cytotoxicity assay employing a specific anti-T-cell serum and by spontaneous rosette formation with sheep erythrocytes (E rosettes). The percentage of T cells in the patients was similar to that of normal subjects as judged by the cytotoxicity assay (65 to 90%). In addition, absolute T-lymphocyte counts were normal in 63% of the patients and were generally reduced only in those with lymphopenia. The percentage of T lymphocytes determined by the E-rosette assay was similar to that determined by the cytotoxicity assay in normal controls, but was significantly lower than that determined by the cytotoxicity assay in the patients. Moreover, the decreased response to PHA stimulation in the patients was directly correlated with the decrease in E-rosette formation. These findings suggest that T lymphocytes in the peripheral blood are not generally diminished in untreated Hodgkin's disease. However, a proportion of these cells exhibits altered surface interactions that may account for some aspects of their impaired immunologic function.

B-Lymphocytes↗
PubMed1975

Maturation of B lymphocytes in the rat. II. Subpopulations of virgin B lymphocytes in the spleen and thoracic duct lymph.

Thoracic duct and spleen cells of normal (unimmunized) adult rats were fractionated according to size by 1 times G velocity sedimentation. Fractions were tested for their ability to restore the adoptive antibody response of irradiated hosts to horse spleen ferritin. A constant source of T cells (small numbers of unfractionated thoracic duct cells) was added to each fraction in order to monitor the B cell activity of the latter. Although large and small cell fractions of the spleen showed restorative activity, only the small cell fractions of the thoracic duct lymph showed activity. The turnover rate of the spleen cell fractions was determined by treating donors with high specific-activity 3H-thymidine for 48 hr before splenectomy. Rapidly dividing cells are preferentially killed by this treatment. The results suggest that a considerable proportion of large, intermediate, and small virgin B cells turn over within 48 hr. The cell surface of the various spleen cell fractions was examined for the presence of immunoglobulin (Ig) and a receptor for complement. The percentage of Ig-bearing cells in the large cell fractions was similar to the percentage of cells bearing IgM and a receptor for complement. However, the majority of Ig-bearing cells in the small cell fractions did not show the latter two surface markers. Experiments with the fluorescence-activated cell sorter showed that the large functionally active B cells bore surface IgM. The experimental findings suggest that there are subpopulations of virgin B cells in the spleen of the adult rat which differ with respect to size, migration pattern, turnover rate, and cell surface characteristics. The relationship of these cells to one another is discussed in the framework of an antigen-independent model of B cell maturation in the rat.

Animals↗
PubMed1975

Immune specific production of interferon by human T cells in combined macrophage-lymphocyte cultures in response to Herpes simplex antigen.

Human peripheral blood lymphocytes, highly enriched for T cells, were obtained by passing gravity-sedimented leukocytes through nylon wool columns. The eluted cells were cultured with autologous macrophages and the mixture was studied for its capacity to produce interferon in vitro in response to stimulation with herpes simplex virus antigen. The interferon produced by the combined macrophage-lymphocyte cultures was shown to depend upon the presence of T cells; elimination of these cells by treatment with an anti-T cell serum plus complement greatly diminished the amount of interferon produced. The memory for the immune-specific release of interferon also appeared to be carried by the T lymphocytes rather than the glass-adherent macrophages. Furthermore, the results suggest that under our conditions of culture immune-specific interferon originates from T cells.

Animals↗