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Biomedical subjects

R Palacios

Publications and source records attributed to R Palacios.

At least 163 records · Page 9Linked to original sources
PubMed1982

Physiology of ammonium assimilation in Neurospora crassa.

In Neurospora crassa the assimilation of high and low concentrations of ammonium occurs by two different pathways. When the fungi are growing exponentially on ammonium excess, this compound is fixed by a glutamic dehydrogenase and an octameric glutamine synthetase (GS). The synthesis of this GS polypeptide (beta) is regulated by the nitrogen source present in excess; being higher on glutamate, intermediate on ammonium, and lower on glutamine. When N. crassa is growing in fed-batch ammonium-limited cultures a different polypeptide of GS (alpha), arranged as a tetramer, is synthesized. In both conditions synthesis in vivo correlates with the data obtained with an in vitro translation system primed with N. crassa RNA. This different expression of alpha and beta GS polypeptides was also observed when the cultures were shifted from excess to low nitrogen, and vice versa. By agarose gel electrophoresis in the presence of methylmercury hydroxide, some separation of different mRNAs that direct the in vitro synthesis of alpha and beta GS polypeptides has been accomplished. Data are presented that establish the operation of the tetrameric alpha GS and of glutamate synthase in the assimilation of ammonium in low concentration.

Ammonium Chloride↗
PubMed1982

Dextran-sulfate: a mitogen for human T lymphocytes.

Dextran-sulfate (DxS) induced proliferation of human peripheral blood T lymphocytes but not of adult or neonatal B lymphocytes. The mitogenic activity on T cells by DxS required the presence of accessory cells because DxS was unable to trigger T cells to DNA synthesis in the absence of accessory cells. In addition, DxS stimulated OKT4+8- T cells to produce interleukin 2, a process that also occurred only in the presence of accessory cells. Cyclosporin-A strongly suppressed T cell proliferation induced by DxS by rendering T cells unresponsive to interleukin 2 and by inhibiting the synthesis of this T cell growth factor by OKT4+ T cells. These results indicate that DxS is a mitogen for human T lymphocytes but not for adult or neonatal B lymphocytes. The mechanism by which DxS triggers T cells is discussed.

Antibodies, Monoclonal↗
PubMed1982

Concanavalin A triggers T lymphocytes by directly interacting with their receptors for activation.

Anti-HLA-DR antibodies did not inhibit concanavalin A-(Con A) induced T cell proliferation or the generation of suppressor cells capable of inhibiting immunoglobulin synthesis in autologous mononuclear cells after pokeweed mitogen stimulation. Nylon-wool purified T cells (pretreated with anti-HLA-DR antibody and C) exposed to Con A acquired responsiveness to interleukin 2 (IL 2) and were able to absorb this growth factor, whereas nonlectin-treated cells did not respond to IL 2 and could not absorb it. In the presence of interleukin 1 (IL 1), Con A stimulated the synthesis of IL 2 in purified OKT4+ lymphocytes but not OKT8+ cells. However, in the absence of IL 1, neither resting OKT4+ nor Con A-treated OKT4+ cells produced IL 2. Con A by itself did not directly stimulate macrophages to synthesize IL 1, although it could do so in the presence of OKT4+ but not OKT8+ lymphocytes. In addition, Con A induced proliferation of purified T cells provided IL 1 was supplied to the cultures. Cyclosporin A rendered Con A-treated T cells unresponsive to IL 2, made lectin-stimulated OKT4+ lymphocytes unable to respond to IL 1, and inhibited the synthesis of IL 2. Furthermore, this drug abrogated the Con A-stimulated synthesis of IL 1 by acting on OKT4+ lymphocytes and not on macrophages. Finally, cyclosporin-A suppressed the proliferative response and the generation of suppressor T cells induced by Con A. The following are concluded: 1) HLA-DR antigens do not seem to play any role in the triggering of T cells by Con A, and macrophages participate in lectin-induced activation of T cells mainly by providing IL 1. 2) Cyclosporin-A inhibits activation of T cells by interfering with the mechanism by which Con A stimulates T lymphocytes. 3) Con A triggers T lymphocytes by directly interacting with their receptors for activation.

Animals↗
PubMed1982

Cyclosporin-A and the OKT3 monoclonal antibody exert their respective inhibitory and mitogenic activity on T cells by interacting with the same receptors.

Cyclosporin-A strongly suppressed proliferation of T cells induced by the OKT3 monoclonal antibody when added at the beginning of the cultures but not when added 72 hr later. The inhibitory activity of Cyclosporin-A became apparent during the first 48 hr and was maintained throughout the culture period. Cyclosporin-A significantly inhibited binding of OKT3, but not OKT4 or OKT8, antibodies to T cells as determined by indirect immunofluorescence microscopy. In addition, Cyclosporin-A suppressed the killing of 51Cr labelled T cells mediated by OKT3 antibody plus complement, whereas Cyclosporin-A did not alter the lysis of T cells by OKT4 antibody plus complement treatment. These results strongly suggest that Cyclosporin-A and OKT3 antibody exert their respective suppressive and mitogenic activity on T cells by interacting with the same receptor.

Antibodies, Monoclonal↗
PubMed1981

T cell growth factor abrogates concanavalin A-induced suppressor cell function.

Concanavalin A (Con-A)-induced suppressor T cells were found to respond to T cell growth factor (TCGF) by proliferation. TCGF abrogated the suppressor activity exerted by these cells on phytohemagglutinin (PHA)- and alloantigen- induced lymphocyte proliferation and on pokeweed mitogen (PWM)-driven immunoglobulin secretion. The Con-A-activated suppressor T cells absorbed the TCGF activity, preincubation of these active suppressor cells with TCGF abolished their suppressor activity and addition of increasing numbers of Con-A-activated T cells reverted the abrogator,/ effect of TCGF. Altogether, these findings suggest that Con-A-induced suppressor T cells exert their function by decreasing the available levels of TCGF. Cyclosporin-A (CYA), which is known to inhibit the expression of receptors for TCGF on T cells, also inhibited the suppressor activity as determined in both indicator systems, namely PHA- or alloantigen-induced DNA synthesis and PWM-induced immunoglobulin synthesis. CYA made Con-A-treated T cells unresponsive to TCGF and unable to absorb the growth factor, supporting the notion that CYA inhibits the expression of TCGF receptors on T cells, a mechanism by which this drug seems to abrogate Con-A-induced suppressor T cell function.

Concanavalin A↗
PubMed1981

Differences in immunoregulatory T cell circuits between diphenylhydantoin-related and spontaneously occurring systemic lupus erythematosus.

We studied T cell surface markers, concanavalin A-induced, and spontaneously expanded suppressor cell function and the functions of postthymic precursor (Tar) cells in 3 patients with diphenylhydantoin (DPH)-related systemic lupus erythematosus (SLE). The findings were compared with those in 6 patients with spontaneously occurring SLE, 3 with active and 3 with inactive disease as well as with those in 3 normal volunteers. All 4 groups were age and sex matched. Findings were also compared to studies made in a group of 32 untreated idiopathic SLE patients and 32 normal controls. All T cell markers and immunoregulatory functions were normal in the DPH-treated SLE patients whereas all groups of patients with spontaneously occurring SLE had low numbers of t gamma cells, and Tar cells, and decreased concanavalin-A and spontaneously expended suppressor, human feedback inhibition and generation of suppression functions. Since consanguineous relatives of patients with spontaneously occurring SLE have been shown to have decreased suppressor cell function and patients with long-inactive spontaneous SLE continue to have defects in their T cell circuits, our findings may indicate that, in patients who develop SLE upon DPH intake the lupus diathesis uncovered by the drug probably resides in a site of immunoregulation different from that involved in spontaneously occurring lupus.

Adolescent↗
PubMed1981

Human postthymic precursor cells in health and disease. IV. Abnormalities in immunoregulatory T cell circuits in mixed connective tissue disease.

Human T cells are capable of forming rosettes with autologous erythrocytes (Tar cells) and behave as postthymic precursors. Thus, they generate Tgamma and Tmu cells as well as suppression and spontaneous cytotoxicity and participate in a pokeweed mitogen-driven system akin to that of feedback inhibition in which murine postthymic precursors participate. Tar cells were increased in 7 patients with mixed connective tissue disease (MCTD) compared to normal age/sex-matched controls. Despite this increase of precursor cells, decreased Tgamma cells and abrogation in the generation of suppression and of feedback inhibition were noted. These functional defects were not correctable with serum thymic factor but could be corrected by the addition of either allogenic Tmu or mononuclear cells depleted of Tar cells. Our findings suggest that the immunoregulatory T cell circuits in MCTD may be adequate both in postthymic precursor cells and in the thymic factor prompting. They are probably abnormal either at the site of Tmu signaling to Tar cells in feedback inhibition or in the Tmu reception of suppressor signals from Tgamma cells. The decrease of Tgamma cells in MCTD could be due to the decreased stimulus from feedback inhibition and/or to the penetration of anti-ribonucleoprotein antibody. Abnormalities of immunoregulatory T cell circuits in MCTD are quite different from those found previously in systemic lupus erythematosus, scleroderma, and rheumatoid arthritis. These differences support the notion that MCTD is a distinct entity.

Female↗
PubMed1981

Role of individual chains of HLA-DR antigens in activation of T cells induced by alloantigens.

The role of HLA-DR antigens in the activation of T cells in the allogeneic mixed lymphocyte reaction (MLR) was studied by using antibodies raised against the alpha, beta or the complex of both chains of the HLA-DR antigens. Antisera directed against the alpha or the beta chain strongly inhibited the T-cell proliferative response when added at the beginning of MLR cultures but not 72 h later. T cells from MLR cultures treated with either alpha-chain- or beta-chain-specific antibodies did not respond to interleukin-2 (IL-2) by proliferating, whereas T cells from non-anti-DR-treated cultures showed a proliferative response to IL-2-stimulation. However, neither the anti-alpha chain nor the anti-beta chain serum was able to inhibit continuous proliferation of already activated, IL-2-reactive T cells supported by IL-2. In MLR, OKT4+ but not OKT8+ lymphocytes synthesized IL-2. This function was abrogated by the alpha-chain-specific antibody but not by the anti-beta chain serum. Interleukin-1 (IL-1) did not reverse the inhibitory activity on IL-2 synthesis of the alpha-chain antibody, while IL-1 promoted the production of IL-2 in MLR cultures not exposed to the anti-DR sera. In addition, nonstimulated OKT4+ cells were unresponsive to IL-1 and did not produce IL-2. From these results, it is concluded that HLA-DR antigens participate actively in the activation of T cells by allogeneic non-T cells. Thus, both the alpha and beta chains of HLA-DR antigens render resting T cells sensitive to IL-2. In addition, the alpha but not the beta chain participates in the production of IL-2 by enabling OKT4+ lymphocytes to respond to IL-1 and subsequently to synthesize IL-2. Once T cells have acquired responsiveness to IL-2 and this growth factor has been produced there is no further requirement for HLA-DR antigens. Continuous proliferation and growth of IL-2-reactive T cells depends on the availability of interleukin-2.

Antibody Specificity↗
PubMed1981

HLA-DR antigens induce proliferation and cytotoxicity of T cells against haptenated (TNP and FITC) self structures.

Antisera directed against the heavy, the light, or reactive against the complex of both chains of HLA-DR antigens strongly inhibited proliferation of T cells induced by TNP- or FITC-labeled autologous cells when added at initiation of the cultures, but not 72 h later. T cells from cultures treated with the anti-DR sera were unresponsive to interleukin-2 (IL-2). Nonetheless, the anti-DR sera did not inhibit proliferation of T cells that had already acquired sensitivity to IL-2. The DR antibodies abrogated the synthesis of IL-2 induced by both TNP-and FITC-conjugated autologous cells. Treatment of TNP-and FITC-labeled autologous cell cultures with the four different types of anti-DR sera significantly inhibited the induction of cytotoxic T cells. However, DR antibodies added at the effector phase of cytotoxicity assays did not inhibit the cytotoxic activity. Effector T cells from cultures treated with the anti-DR sera were unresponsive to IL-2 and addition of IL-2 to these cultures did not restore the cytotoxic activity. In contrast, effector T cells from cultures performed in the absence of the anti-DR sera proliferated to Il-2 stimulation and addition of IL-2 to these cultures significantly increased the generation of killer cells specific for hapten-labeled self structures. From these results we concluded the following: (1) Both the heavy and the light chains of Dr antigens participate actively in the activation of T cells by rendering resting T cells sensitive to IL-2 and by inducing production of the growth factor in TNP-and FITC-conjugated autologous cell cultures. (2) The heavy and light chains of the DR antigens play an essential role in the induction of cytotoxic T cells specific for hapten-labeled self structures, most likely by enabling cytotoxic T cells to respond to Il-2 and by inducing the IL-2 producer T cells to synthesize the growth factor.

Cytotoxicity, Immunologic↗