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Biomedical subjects

S Strober

Publications and source records attributed to S Strober.

At least 145 records · Page 8Linked to original sources
PubMed1982

Spleen cells from adult mice given total lymphoid irradiation (TLI) or from newborn mice have similar regulatory effects in the mixed leukocyte reaction (MLR). II. Generation of antigen-specific suppressor cells in the MLR after the addition of spleen cells from newborn mice.

Spleen cells from newborn BALB/c mice were added to the mixed leukocyte reaction (MLR) between a variety of responder and stimulator cells. The newborn cells nonspecifically suppressed the uptake of (3H)-thymidine and the generation of cytolytic cells regardless of the responder-stimulator combination used. Suppressor cell activity fell rapidly during the first 4 days after birth, and could not be detected by day 20. Newborn spleen cells inhibited the generation of nonspecific suppressor cells during the MLR but did not inhibit the generation of antigen-specific suppressor cells. Thus, newborn spleen cells exhibit a pattern of regulation of the MLR similar to that reported previously for spleen cells from adult mice given total lymphoid irradiation (TLI). These regulatory interactions provide a model that explains the ease of induction of transplantation tolerance in vivo in newborn mice and in TLI-treated adult mice.

Animals↗
PubMed1982

LPS-induced differentiation of a murine B cell leukemia (BCL1): changes in surface and secreted IgM.

We examined the effect of LPS-induced differentiation on surface and secreted IgM in a cloned BCL1 in vitro cell line. Incubation of this cell line with LPS resulted in a decrease in the amount of membrane IgM, measured by both immunofluorescence and immunoprecipitation, and an increase in IgM secretion, measured by plaque-forming cells (PFC). Activation to high rate secretion was independent of cell cycle in synchronized cells and was independent of DNA synthesis because PFC formation was not inhibited by hydroxyurea. Almost all cells in the in vitro line were shown to contain large quantities of intracytoplasmic IgM before LPS activation. Thus, it would appear that the in vitro cell line represents a partially activated stage of differentiation compared to normal resting B cells or to the in vivo line of BCL1. Analysis of the two forms of mRNA coding for membrane and secreted IgM showed that, at least for cells at the level of differentiation examined here, the control of membrane IgM expression is post-transcriptional. The differentiation of resting B cells to the plasma cell level appears to consist of multiple stages of differentiation. The present data suggest that LPS provides at least two signals of activation. One induces the resting cell to synthesize cytoplasmic IgM, increase surface IgM, and to begin cell division. The second induces the secretion of intracytoplasmic IgM associated with a decrease in surface IgM.

Animals↗
PubMed1981

Treatment of intractable rheumatoid arthritis with total lymphoid irradiation.

Eleven patients with intractable rheumatoid arthritis were treated with total lymphoid irradiation (total dose, 2000 rad) in an uncontrolled feasibility study, as an alternative to long-term therapy with cytotoxic drugs such as cyclophosphamide and azathioprine. During a follow-up period of five to 18 months after total lymphoid irradiation, there was a profound and sustained suppression of the absolute lymphocyte count and in vitro lymphocyte function, as well as an increase in the ratio of Leu-2 (suppressor/cytotoxic) to Leu-3 (helper) T cells in the blood. Persistent circulating suppressor cells of the mixed leukocyte response and of pokeweek mitogen-induced immunoglobulin secretion developed in most patients. In nine of the 11 patients, these changes in immune status were associated with relief of joint tenderness and swelling and with improvement in function scores. Maximum improvement occurred approximately six months after irradiation and continued for the remainder of the observation period. Few severe or chronic side effects were associated with the radiotherapy.

Antibodies, Monoclonal↗
PubMed1981

Immunoregulatory changes induced by total lymphoid irradiation. II. Development of thymus-leukemia antigen-positive and -negative suppressor T cells that differ in their regulatory function.

BALB/c mice treated with total lymphoid irradiation (TLI) develop non-antigen-specific suppressor cells of the adoptive secondary antibody response and of the mixed leukocyte reaction. Suppressors of the adoptive anti-DNP response were eliminated by incubation of spleen cells with anti-Thy-1.2 or anti-thymus-leukemia (TL) antiserum and complement before cell transfer. Thymectomy before TLI prevented the appearance of the latter suppressor cells. On the other hand, suppressors of the MLR were eliminated by incubation of spleen cells with anti-Thy-1.2 but not anti-TL antiserum and complement. Thymectomy before TLI did not prevent their subsequent development. Thus, two subpopulations of suppressor T cells that differ in the expression of the TL surface antigen, dependence on the presence of the thymus, and in regulatory functions develop after TLI. The TL+, thymus-dependent cell suppresses the adoptive antibody response, and the TL-, thymus-independent cell suppresses the MLR.

Animals↗
PubMed1981

'Managing' the immune system with total lymphoid irradiation.

Total lymphoid irradiation (TLI), which in the past was limited to the treatment of malignant disease, is now emerging as a practical technique in the management of unwanted immune reactions in the areas of transplant tolerance and various autoimmune diseases. Current studies are particularly promising for application of TLI in rheumatoid arthritis and lupus nephritis.

Arthritis, Rheumatoid↗
PubMed1981

Survival of primates following orthotopic cardiac transplantation treated with total lymphoid irradiation and chemical immune suppression.

Fractionated total lymphoid irradiation (TLI) has been used for attempts at induction of a donor-specific tolerant-like state in allograft recipients and for immunosuppressive effects. Cyclosporin A (Cy A) has been shown to suppress rejection of organ grafts in many species including man. The present study was designed to test the effectiveness of TLI in combination with either CY A or rabbit anticynomolgus thymocyte globulin (ATG) and azathioprine. Thirty-one orthotopic cardiac allografts were performed using surface cooling and total circulatory arrest in outbred cynomolgus monkeys. TLI was administered preoperatively in fractions of 100 rad until a total of 600 or 1800 rad was achieved. Cy A was administered 17 mg/kg/day. All treatment groups demonstrated extended survival. Myocardial biopsies as early as 4 weeks were consistent with mild rejection in all treatment groups. No significant synergistic effect upon survival could be demonstrated utilizing TLI plus Cy A when compared with using Cy A alone. TLI (1800 rad) plus ATG and azathioprine was associated with a high incidence of early death attributable to leukopenia and infection. Cy A alone or in combination with TLI was associated with the development of lymphoid malignancy.

Animals↗
PubMed1981

In-vitro T cell mediated function in patients with active rheumatoid arthritis.

In-vitro synthesis of peripheral blood lymphocytes from patients with rheumatoid arthritis was measured after stimulation with phytohaemagglutinin (PHA) in a short-term, serum-free culture system. Diminished responses were found in 16 out of 17 consecutive patients with active disease. Normal PHA responsiveness was recovered by assaying Ficoll-Hypaque isolated E rosette forming cells in serum-free medium, indicating basically normal T cell function in RA. Preincubation of normal peripheral blood lymphocytes (or isolated E rosette forming cells) with sera obtained from patients with active RA for 30 minutes at 4 degrees C or 37 degrees C blocked PHA responsiveness in 34 out of 43 tests. This suggests that serum blocking factors may be responsible for reduced T cell reactivity in RA.

Arthritis, Rheumatoid↗
PubMed1981

The relationship between surface immunoglobulin isotype and the immune function of murine B lymphocytes. V. High affinity secondary antibody responses are transferred by both IgD-positive and IgD-negative memory B cells.

We examined the adoptive secondary anti-DNP responses restored by surface IgD+ and IgD- memory B cells. Several parameters that might affect the affinity and magnitude of the adoptive responses were studied: 1) time after priming of cell donors, 2) source of anti-IgD antibodies used for immunofluorescent cell staining, 3) adjuvant used for priming, 4) carrier protein used for priming, 5) amount of antigen used for the challenge of adoptive hosts, and 6) the strain of ice used as donors and recipients. In contrast to previous reports, the present results demonstrate that the selection of cells with high affinity antigen receptors can occur to the same extent in both the delta + and delta - memory cell pools. This suggests that the loss of surface IgD is not a necessary intermediate stage in the maturation of memory B cells.

Animals↗
PubMed1981

Immunoglobulin class commitment exhibited by B lymphocytes separated according to surface isotype.

In order to determine the extent to which B cells exhibit class commitment, the isotype(s) secreted by individual B cells and their progeny was studied in relation to the isotype(s) expressed on the surface of the B cell. Both primary and secondary B cells were separated according to cell surface isotypes and analyzed under optimal stimulation conditions using the T-dependent splenic focus assay. From these studies the following conclusions conclude be made: a) essentially all mature primary B cells appear to express mu on their surface; b) accordingly, the primary B cell population appears to be devoid of B cells expressing solely IgG on their surface; c) the majority of primary B cells in the presence of optimal T cell help have the potential for multiple class production; d) the secretion of IgA coincides with that of IgM and not IgG in its synthesis by immature B cells; e) a substantial proportion of memory B cells bear mu on their surface; f) memory B cells that lack s-mu are unable to yield clones secreting IgM; and g) a substantial proportion of memory B cells have the potential for multiple class production.

Animals↗
PubMed1981

Immunoregulatory changes induced by total lymphoid irradiation (TLI). I. Appearance of a population of cells bearing the thymus leukemia (TL) surface antigen in the lymph nodes and spleen.

BALB/c mice were treated with total lymphoid irradiation (TLI; 3400 rads) or single-dose, whole-body irradiation (WBI; 550 rads), and the lymph nodes and spleen were assayed for the level of H-2, Ia, Thy-1.2, Lyt-1.2, Lyt-2.2,3.2, and TL-bearing cells by an in vitro cytotoxicity assay. The level of cells bearing all these markers, except for TL, was similar to that observed in normal unirradiated mice. The level of TL+ cells was increased 10- to 20-fold in the TLI-treated mice as compared to WBI-treated mice or normals. The increased number of TL+ cells persisted for at lest 200 days after radiotherapy, and was not dependent upon irradiation of the thymus. However, thymectomy before TLI prevented the subsequent development of peripheral TL+ cells. The findings suggest that this abnormal subpopulation of T cells develops as a result of changes in the peripheral lymphoid tissue microenvironment induced by TLI.

Animals↗
PubMed1980

Cellular basis of graft versus host tolerance in chimeras prepared with total lymphoid irradiation.

BALB/c mice given allogeneic (C57BL/Ka) bone marrow cells after toal lymphoid irradiation become stable chimeras approximately 80% donor-type and 20% host-type cells in the spleen. The chimeras doe not develop graft vs. host disease (GVHD). Purified cells of C57BL/Ka origin from the chimeras mediated GVHD in lightly irradiated C3H (third party), but not in BALB/c (host-strain) mice. Thus graft vs. host tolerance in the chimeras could not be explained by complete immunodeficiency of donor-type cells, serum blocking factors, or suppressor cells of host (BALB/c) origin. Clonal deletion or suppression of lymphocytes reactive with host tissues remain possible explanations. The transfer of donor-type chimeric spleen cells to BALB/c recipients given 500-550 rad whole-body irradiation WBI led to stable mixed chimerism in approximately 50% of recipients. The cells were presumably acting as tolerogens because similarly irradiated BALB/c mice given (BALB/c X C57BL/Ka)F1 spleen or bone marrow cells also became stable mixed chimeras.

Animals↗