Search PubMed⌕ Search

Biomedical subjects

S Strober

Publications and source records attributed to S Strober.

At least 37 records · Page 2Linked to original sources
PubMed1992

Studies of CD4- CD8- alpha beta bone marrow T cells with suppressor activity.

The predominant T cell subset in the bone marrow of specific pathogen-free C57BL/Ka and BALB/c mice expressed the alpha beta+ TCR CD4- CD8- surface phenotype. Purified C57BL/Ka alpha beta+ TCR CD4- CD8- marrow cells obtained by cell sorting suppressed the MLR of C57BL/Ka responder and BALB/c stimulator spleen cells. Although the percentage of typical T cells in the spleen was markedly reduced in adult nude mice or normal neonatal mice as compared to the normal adult, the percentage of alpha beta+ TCR CD4- CD8- cells in the spleen and marrow was not. The percentage of "self-reactive" V beta 5+ T cells in the BALB/c spleen was markedly reduced as compared to that in the C57BL/Ka spleen. However, the percentages in the bone marrow were similar. The results indicate that the predominant subset of marrow T cells in these pathogen-free mice differ with regard to surface marker phenotype, function, dependence on the adult thymus, and deletion of certain self-reactive V beta receptors as compared to typical spleen T cells. The marrow T cells appear to develop directly from marrow precursors without rearranged beta chain genes during a 48 hour in vitro culture.

Animals↗
PubMed1991

Thymic irradiation inhibits the rapid recovery of TH1 but not TH2-like functions of CD4+ T cells after total lymphoid irradiation.

Four to six weeks after total lymphoid irradiation (TLI), there is a selective deficit in the CD4+ T cells which secrete IL-2, proliferate in the MLR, and induce GVHD (Th1-like functions). A similar deficit in CD4+ T cells which secrete IL-4 and help antibody responses (Th2-like functions) is not observed. In the present study, shielding of the thymus with lead during TLI increased the Th1-like functions of CD4+ cells. Mice without thymus shields showed a marked selective reduction in the medullary stromal cells identified with the monoclonal antibody, MD1, and the severe reduction was prevented with thymus shields. Thus, shielding the thymus prevents the depletion of thymic medullary stromal cells and allows for a rapid recovery of Th1-like functions in the mouse spleen after TLI. Th2-like functions recover rapidly after TLI whether or not the thymus is irradiated.

Animals↗
PubMed1991

T lymphocyte-synovial fibroblast interactions induced by mycobacterial proteins in rheumatoid arthritis.

An in vitro system was established in which single-cell suspensions of lymphocytes and synovial cells from the joints of patients with rheumatoid arthritis were cultured and produced an outgrowth of an organized inflammatory tissue with an extracellular matrix and capsule. The tissue outgrowth, which had histologic features of pannus, required the addition of mycobacterial antigen and interleukin-2 to the tissue culture medium and was dependent upon the presence of T lymphocytes and their interaction with synovial fibroblasts.

Arthritis, Rheumatoid↗
PubMed1991

Identification of a factor(s) from cloned murine natural suppressor cells that inhibits IL-2 secretion during antigen-driven T cell activation.

Crude supernatants were obtained from cloned murine natural suppressor (NS) cells activated in vitro with phorbol-myristate-acetate (PMA) and calcium ionophore (A23187). Supernatants suppressed IL-2 production in the mixed leukocyte reaction (MLR) with BALB/c spleen cells, but no reduction was observed in the response to PHA, Con A, or anti-CD3 antibody. Suppressive activity was partially purified by DEAE ion exchange chromatography, and inhibited the antigen-presenting function of the macrophage line 1G18-LA in an assay system with the ovalbumin-specific T cell hybridoma, 3DO-18.3. In addition, the antigen-presenting function of the A20 B cell line was inhibited in an assay with a sperm whale myoglobin (SpWMb)-specific T cell hybridoma (8.2.1d.H1a). Results with blocking antibodies suggest that this factor appears to be a unique cytokine.

Animals↗
PubMed1991

Regulation of thymocyte proliferation by alpha beta TcR+ CD3+ CD4- CD8- cloned natural suppressor (NS) cells.

Cloned alpha beta TcR+ CD3+ CD4- CD8- T cells, with natural suppressor (NS) activity, were cocultured with thymocytes in the presence or absence of mitogen or cytokines. Whereas thymocytes show a minimal response to phytohemagglutinin (PHA), IL-2, or IL-4 alone, they proliferate vigorously when cocultured with irradiated cloned NS cells in the presence of PHA or IL-2 or IL-4, but not with IL-1, IL-3, IL-6, IL-7, IFN-gamma, or GM-CSF. Among a total of 11 NS cell clones, derived from the spleen or thymus, only one clone (NR-1) did not induce thymocyte activation in synergy with PHA. This costimulation is most likely mediated by soluble factor(s), since supernatants, obtained from NS cells activated with phorbol ester (PMA) and calcymicin (A23187) or with solid phase anti-CD3 mAb, enhance thymocyte DNA synthesis in the presence of a mixture of PHA, IL-2, and IL-4. The latter factor does not appear to be a previously described lymphokine, since PMA- and A23187-activated NS cells secrete IL-3, TGF-beta, IFN-gamma, GM-CSF, and TNF-alpha, but not IL-1, IL-2, IL-4, IL-5, IL-6, IL-7, nor IL-10. None of the factors, identified in the NS cell supernatants, was able to stimulate thymocyte DNA synthesis. This study shows that, in addition to their previously reported suppressor function, cloned NS cells can exert immunostimulatory activities by virtue of a soluble mediator.

Animals↗
PubMed1991

Extent of glomerular injury in active and resolving lupus nephritis: a theoretical analysis.

Patients with diffuse, proliferative lupus nephritis (DPLN) were subjected to differential solute clearances (n = 22) and serial renal biopsy (n = 11) before and again after 6-12 mo of immunosuppressive therapy. Glomerular sieving of dextrans of graded size was analyzed with a heteroporous membrane model. This revealed active DPLN to be associated with 1) a reduction of overall pore density accompanied by a 53% depression of glomerular filtration rate (GFR), and 2) appearance of a subset of large, nondiscriminatory pores, which accounted for the observed nephrotic level of proteinuria. Morphometric analysis of biopsy tissue provided evidence of reduced filtration surface area due to global or segmental occlusion of capillary loops in glomerular tufts. Activity of DPLN resolved posttreatment. A computed increase in pore density was associated with a 24% increment in GFR; a marked reduction in the fraction of shuntlike pores was accompanied by a parallel reduction of proteinuria into a subnephrotic range. Repeat biopsy revealed diminished glomerular cellularity, fewer immune deposits, and an ensuing increase in the fraction of tuft area occupied by patent loops. Epithelial filtration slit frequency also increased. Neither functional nor structural recovery was complete, however. Residual pore density approximated only 23-35% of that in healthy controls, and corresponding shuntlike pores were threefold more prominent. We conclude that severe DPLN is only partially reversible by current modalities of treatment and that the ensuing residual injury is far more severe than suggested by conventional tests of renal function.

Adolescent↗
PubMed1990

Ly-1 B cells and disease activity in (New Zealand black x New Zealand white)F1 mice. Effect of total lymphoid irradiation.

The treatment of female (New Zealand black x New Zealand white)F1 mice with total lymphoid irradiation resulted in a prolonged remission of autoimmune disease activity. Total lymphoid irradiation-treated mice also showed a marked reduction of Ly-1 B cells, which lasted up to 3 months. The subsequent return of Ly-1 B cells to preirradiation levels was not associated with a simultaneous return of disease when measured by parameters such as IgG anti-DNA antibodies and spontaneous secretion of IgG by splenic cells. In cell sorting experiments, most of the cells spontaneously secreting IgG were found within the Ly-1- (CD5-) splenic B cell population.

Animals↗
PubMed1990

B cell infiltration of the thymic medulla in New Zealand black, New Zealand white, and (New Zealand black x New Zealand white)F1 mice. Effect of total lymphoid irradiation.

Thymuses from female (New Zealand black x New Zealand white)F1 [( NZB x NZW]F1), New Zealand black, and New Zealand white mice of different ages were examined by immunohistochemical and flow cytometric analysis. Two-and-a-half-month-old (NZB x NZW)F1 mice showed infiltration of the thymus with B cells, and by 6-8 months of age, showed a disruption of the entire medullary area. More than 80% of the thymic B cells had the phenotypic characteristics of conventional B cells (IgM+, IgD+, Ly-1-). Total lymphoid irradiation induced a marked depletion of medullary B cells and a restoration of the thymic architecture.

Animals↗
PubMed1990

Deficits in T helper cells after total lymphoid irradiation (TLI): reduced IL-2 secretion and normal IL-2 receptor expression in the mixed leukocyte reaction (MLR).

Spleen cells from BALB/c mice treated with total lymphoid irradiation (TLI) and from normal, unirradiated mice were compared in the mixed leukocyte reaction (MLR). Although the percentage of CD4+ cells in the spleen was close to normal, 4 to 6 weeks after TLI, the MLR of unfractionated spleen cells from irradiated mice was more than 10-fold lower than controls. A similar reduction was observed when purified CD4+ cells were used as responders in the MLR. Secretion of IL-2 by cells from irradiated mice was also about 10-fold lower than controls. However, the percentage of CD4+ and CD8+ cells which expressed IL-2 surface receptors during the MLR was similar using spleen cells from irradiated and control mice. Addition of an exogenous source of IL-2 restored the proliferative capacity of the irradiated cells and suggests that the lack of IL-2 secretion is the likely explanation of the marked deficit in the MLR of CD4+ spleen cells after TLI.

Animals↗
PubMed1990

Mechanisms of immune injury in rheumatoid arthritis: evidence for the involvement of T cells and heat-shock protein.

Evidence for the involvement of T cells, especially CD4+ T cells, in the pathogenesis of RA is substantial and includes 1) the correlation between prolonged CD4+ T-cell depletion and improvement in joint disease in the absence of observable changes in the levels of autoantibodies (rheumatoid factors) in the blood and joints, 2) the infiltration of the inflamed synovial tissues with T cells and, 3) the increased susceptibility of individuals to RA with certain HLA-DR haplotypes. The most direct evidence for the involvement of CD4+ T cells is provided by recent studies which demonstrate rapid improvement in the joint disease manifestations of RA following the infusion of anti-CD4 monoclonal antibodies (Herzog et al. 1989, Walker et al. 1989). It is unlikely that T cells alone are responsible for the joint injury in RA. Autoantibodies (rheumatoid factors) in the joint which contribute to the release of complement breakdown products, and to the secretion of cytokines such as IL-1 by macrophages must also play an important role. Indeed, depletion of CD4+ cells after TLI or therapy with monoclonal antibody reduces, but does not eliminate, joint disease activity. The residual joint disease activity is probably influenced by the continued contribution of autoantibodies to joint injury. Production of these autoantibodies may not be dependent on help from CD4+ cells, since little change is observed in autoantibody levels after CD4+ cell depletion. The mechanisms by which T cells mediate to the joint disease in RA are not clear. Little or no direct evidence of cytotoxic effects of T cells on autologous joint cells has been reported. Considerable evidence suggests that at least some T-cell cytokines (i.e., TNF alpha, IL-6) can contribute to the proliferation of synovial lining cells which results in the marked build-up of inflammatory tissue (pannus) in the joints of patients with RA (Firestein et al. 1990). In addition, T cells may recruit other joint cells, such as macrophages, to secrete cytokines (i.e., IL-1) which both contribute to synovial cell proliferation, and cartilage and bone degeneration. The marked reduction in the spontaneous secretion of IL-1 by synovial biopsies, and improvement in disease activity after TLI support this notion. Interestingly, the CD4+ T-cell lymphokines, IL-2 and IFN-gamma, were not spontaneously secreted in detectable quantities by synovial biopsies. This suggests that the pattern of lymphokines secreted by T cells in the joint in RA are not typical of that in delayed-type hypersensitivity reactions.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1990

Recognition of self class II major histocompatibility complex antigens by CD8+ T cell clones derived from rheumatoid arthritis synovial membrane.

T cells from rheumatoid synovium have been expanded in vitro as lines and clones using autologous Epstein-Barr virus-transformed stimulator cells. Both lines and clones recognized autologous class II MHC antigens in the absence of defined exogenous antigens i.e. the equivalent of the autologous mixed lymphocyte response. Surprisingly, despite their MHC specificity, several clones expressed CD8 rather than CD4, but were not cytotoxic. The function of CD8+ T cells within synovium has not previously been defined; in view of their unusual phenotype, they may exert an immuno-modulating role upon the inflammatory response within the joint, by responding to the high density of class II MHC antigens expressed in the rheumatoid synovium.

Antigen-Presenting Cells↗
PubMed1989

Evidence for mouse Th1- and Th2-like helper T cells in vivo. Selective reduction of Th1-like cells after total lymphoid irradiation.

Purified CD4+ BALB/c spleen T cells obtained 4-6 wk after total lymphoid irradiation (TLI) helped normal syngeneic B cells to produce a vigorous antibody response to TNP keyhole limpet hemocyanin in adoptive cell transfer experiments. However, the same cells failed to transfer delayed-type hypersensitivity to the adoptive hosts as measured by a foot pad swelling assay. In addition, purified CD4+ cells from TLI-treated mice were unable to induce graft vs. host disease in lethally irradiated allogeneic C57BL/Ka recipient mice. In response to mitogen stimulation, unfractionated spleen cells obtained from TLI mice secreted normal levels of IL-4 and IL-5, but markedly reduced levels of IL-2 and INF-gamma. A total of 229 CD4+ clones from spleen cells of both normal and TLI-treated mice were established, and the cytokine secretion pattern from each clone was analyzed. The results demonstrate that the ratio of Th1- and Th2-like clones in the spleens of normal BALB/c mice is 1:0.6, whereas the ratio in TLI mice is approximately 1:7. These results suggest that Th2-like cells recover rapidly (at approximately 4-6 wk) after TLI treatment and account for the early return of antibody helper activity and secretion of IL-4 and IL-5, but Th1-like cells recover more slowly (in approximately 3 mo) after irradiation, and this accounts for the deficit in cell-mediated immunity and the reduced amount of IL-2 and IFN-gamma secretion.

Animals↗
PubMed1989

Cloned natural suppressor cell lines express the CD3+CD4-CD8- surface phenotype and the alpha, beta heterodimer of the T cell antigen receptor.

Several cloned lines of natural suppressor (NS) cells were studied for their expression of the TCR complex. Almost all bore the CD3+CD4-CD8- surface phenotype with the alpha, beta TCR as judged by immunofluorescent staining. Immunoprecipitation experiments showed a spot on two-dimensional gels which is characteristic of the TCR heterodimer, but neither gamma- nor delta-chains could be precipitated with the appropriate antibodies. NS cells were stimulated to proliferate in vitro with anti-CD3 antibodies and PMA in the presence of irradiated spleen cells. However, anti-CD3 antibodies did not inhibit the suppressive activity of the NS cells. The role of the TCR complex in the suppressive function of these cells remains to be elucidated.

Animals↗