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1.
The role of interferon-alpha (IFN-alpha) and interferon-gamma (IFN-gamma) in the regulation of B-cell function was studied using highly purified tonsillar B-cells and unfractionated mononuclear cells from healthy adults and newborns. Recombinant IFN-gamma (rIFN-gamma) was found to enhance Staphylococcus aureus Cowan I (SAC)-induced proliferation of purified B-cells. Recombinant IFN-alpha (rIFN-alpha) neither enhanced nor inhibited the function of purified B-cells. However, when unfractionated mononuclear cells were studied, no enhancement in SAC- or pokeweed mitogen (PWM)-induced proliferation was found in response to these IFNs. In fact, the responses in these cultures were mainly inhibitory. The effects were dependent on the mitogen used for activation of the cells and on the source of the cells. The IFNs acted in a more inhibitory way in cultures stimulated with PWM than in those stimulated with SAC. In addition, they acted more suppressively in cord blood mononuclear cells (CBMCs) than in adult peripheral blood mononuclear cells. PWM was found to decrease CD4+/CD8+ T-cell ratio, and cells with suppressor function physiologically dominate among CBMCs. Thus, the effect of these interferons on B-cell function seems to depend on the magnitude of suppressor cell function among the cell population.  相似文献   

2.
In vitro production of IgG and IgM from peripheral blood lymphocytes and B-cell enriched fractions was assessed in a group of Hodgkin's disease (HD) patients and normal controls using pokeweed mitogen (PWM) stimulation. Our studies demonstrated a significant (P less than 0.01) reduction in the absolute number of helper (OKT4 positive) T cells and a significant alteration in the helper/suppressor T-cell ratio (0.89 +/- 0.15) compared to normal (1.83 +/- 0.31). Results from PWM stimulation experiments demonstrated that HD patients produced significantly lower IgG (P less than 0.01) and IgM (P less than 0.01) levels than controls. Synthesis of IgM but not IgG induced by PWM was subnormal after addition to patient B-cell cultures of autologous irradiated T cells or allogeneic irradiated normal T lymphocytes. Irradiated T cells from HD patients were as effective as normal T cells in helping PWM induced IgG and IgM synthesis by normal B cells. Our results suggest that in HD impaired circulating B-cell function is partly due to T-suppressor cell activity and furthermore that B-cell subpopulations producing different immunoglobulin isotypes may either be defective or vary in their susceptibility to T-cell suppression.  相似文献   

3.
The present study examines the role of monocytes in the in-vitro activation of human T cells and B cells by pokeweed mitogen (PWM). The T cell-dependent PWM-induced B-cell activation process was found to be monocyte dependent. Fluorescence-activated cell sorter (FACS) analysis revealed that upon addition to peripheral blood mononuclear cells, fluoresceinated PWM, at concentrations that provided optimal B-cell and T-cell activation, bound predominantly to human monocytes. The binding of PWM to monocytes was reversible and could be displaced within the first few hours of binding by oligomers of N-acetylglucosamine (GlcNAc). As a functional correlate of the binding studies, it was shown that PWM-pulsed monocytes could induce B lymphocytes to become plaque-forming cells (PFC) and T lymphocytes to undergo proliferation. In contrast, markedly reduced PFC and blastogenic responses were observed when monocyte-depleted B lymphocytes and T lymphocytes were respectively pulsed with PWM and washed, followed by the addition of non-PWM-pulsed monocytes to the cultures. Thus, the initial event in the PWM-induced activation of human lymphocytes, for both in-vitro T-lymphocyte blastogenic responses and B-lymphocyte Ig secretion, appears to be binding of the mitogen to sugar residues on the surface membrane of the monocyte, followed by subsequent interaction with the appropriate lymphocytes. The process of PWM binding to monocytes did not appear to affect the baseline production of interleukin-1 (IL-1) by human monocytes, nor could soluble factors from PWM-pulsed monocytes substitute for intact cells in the initiation of the lymphocyte-activation process.  相似文献   

4.
Synergistic effects of B-cell mitogen Staphylococcus bacteria strain Cowan I (Cowan I) plus T-cell activator pokeweed mitogen (PWM) in generating immunoglobulin-secreting cells (ISC) from human peripheral blood mononuclear cells (MNC) were investigated. ISC were assayed by reverse plaque-forming cells using protein A-coated red blood cells. Low concentrations of PWM plus Cowan I gave superadditive effects on ISI induction, generating 3–20 times as many ISC as optimal amounts of either mitogen alone. The mitogens together and separately showed similar kinetics of ISC; synergy was observed at every day tested. IgM ISC represented 10% of initial MNC from all cell donors tested even if the donors were low responders to either mitogen alone. The numbers of ISC obtained are higher than previous reports and more uniform among donors, making this a superlative method for studies on normal human immunoglobulin secretion.  相似文献   

5.
The ligation between Leucocyte-Function-Associated Molecule I (LFA-1) and Intercellular Adhesion Molecules (ICAM) is thought to be an important component in the stimulatory interaction between antigen-presenting cells (APC) and T cells. Similar to antigenic stimulation, T-cell stimulation with pokeweed mitogen (PWM) is highly dependent on monocytes as accessory cells. This is partly a consequence of the requirement for mitogen presentation by the monocytes. The study described here addressed the question of whether LFA-1 ligation by accessory cells influences the activation of T cells with PWM. To avoid multiple costimulatory interactions between T cells and monocytes. experiments were performed with purified T cells, which were stimulated with PWM bound on autologous red blood cells (PWM-RBC). Binding on the RBC substituted partly for PWM presentation by the monocytes. Anti-LFA-1 MoAbs were presented in the immobilized form in order to mimick LFA-1 ligation by cell-bound ICAM. Three out of three different MoAbs against the β-chain of the LFA-1 molecule (CD18) and two out of three MoAbs against the α-chain (CD11a) had an enhancing effect on T-cell proliferation, Proliferation was increased further by simultaneous addition of interleukin (IL)-1 β and IL-6. Ligation of the LFA-1 molecule was found to enhance IL-2 production and tumour necrosis faclor-α (TNF-α) production. The results suggest that interaction of LFA-1 with ICAM on the monocytes contributes to the accessory signal activity of monocytes in T-cell activation with PWM.  相似文献   

6.
Human peripheral blood B-cells can be stimulated with PWM and antigen to produce specific antibody in vitro. This stimulation depends on the presence of T-cells and antigen. T cells, however, can be replaced by a soluble factor derived from a 48-hr culture of T-cells with either PWM and/or antigen. The helper factor, in the absence of antigen, acts as a polyclonal activator causing minimal proliferation of B-cells. When antigen is present, production of specific antibody is not dependent on the source of helper factor. Removal of monocytes abolished synthesis of both Ig and specific antibody although antigen and/or helper factor were present. While production of total IgG required autologous monocytes, the origin of the helper factor was not crucial. Production of specific antibody required that both monocytes and helper factor be derived from the same donor; therefore it seems that cooperation of B-, T-cells and monocytes for production of specific antibody is probably Ia restricted. In contrast, for production of polyclonal Ig (in the absence of antigen), cooperation of B-cells and monocytes with T-cells is not.  相似文献   

7.
Human peripheral blood B-cells can be stimulated with PWM and antigen to produce specific antibody in vitro This stimulation depends on the presence of T-cells and antigen. T cells, however, can be replaced by a soluble factor derived from a 48-hr culture of T-cells with either PWM and/or antigen. The helper factor, in the absence of antigen, acts as a polyclonal activator causing minimal proliferation of B-cells. When antigen is present, production of specific antibody is not dependent on the source of helper factor. Removal of monocytes abolished synthesis of both Ig and specific antibody although antigen and/or helper factor were present. While production of total IgG required autologous monocytes, the origin of the helper factor was not crucial. Production of specific antibody required that both mnocytes and helper factor be derived from the same donor; therefore it seems that cooperation of B-, T-cells and monocytes for production of specific antibody is probably Ia restricted. In contrast, for production of polyclonal Ig (in the absence of antigen), cooperation of B-cells and monocytes with T-cells is not.  相似文献   

8.
9.
The membrane molecule termed "7F7-antigen" has been found to be involved in several examples of cell-cell interactions. This 85 kDa glycoprotein with a protein core of about 55 kDa contains N-linked and O-linked carbohydrates. It has an isoelectric point of 8.0-8.5 and is expressed on 20% of peripheral blood mononuclear cells, 35% of peripheral blood B-cells, follicular dendritic cells and vascular endothelium. It is also expressed on activated T-cells and its expression on B-cells, fibroblasts and monocytes increases after treatment with PWM, interferon-gamma and after three days culture, respectively. The MAb 7F7 used to define this antigen inhibits the initiation of T-cell proliferation induced by anti-CD3, PHA, ConA and (weakly) allogenic stimulator cells, but does not affect the growth of IL-2 dependent T-cells and does not interfere with the killing of PHA-blasts by allogenic IL-2 dependent T-cells. 7F7 also inhibits the binding of C3-coated sheep erythrocytes to B-cells, the PMA-induced aggregation of U937 and the binding of activated T-cells to fibroblasts. The 7F7-antigen is expressed on some non-Hodgkin lymphomas of B-cell differentiation, particularly those with follicular structure, but not on Burkitt's lymphoma, ALL or carcinomas of various tissues. It is, however, found on fibrous tissue surrounding infiltrating carcinoma cells. The expression of a melanoma antigen, P3.58, which was shown to be identical to 7F7-antigen correlates with stage and spread of invasive melanoma. It was concluded that the 7F7-antigen, which is probably related to a previously described adherence molecule (ICAM-1), is of biological importance for the initiation of T-cell responses. With the possible exception of melanoma its expression on neoplastic cells in vivo is unlikely to be of importance for the spread of malignant disease.  相似文献   

10.
The suppressive effects of ATP on murine T-cell functions were studied. The suppressive effects of ATP as well as adenosine on the DNA synthesis of spleen cells are due to the presence of mature T-cells, because ATP has no suppressive effect on athymic nu/nu spleen cells. Further characterization of the cells which are responsible for ATP-mediated suppression of DNA synthesis revealed that the cells are nylon wool-adherent T-cells and PHA-reactive T-cells. In addition, the suppressive effects of ATP on both spontaneous and mitogen-induced proliferative responses are stronger than that of adenosine, and T-cells are more sensitive to ATP than B-cells. The observation that both ATP and adenosine have unique effects on T-cells compared to B-cells may contribute toward explaining why patients with severe combined immunodeficiency (SCID) associated with adenosine deaminase (ADA) deficiency have greater T-cell than B-cell abnormalities.  相似文献   

11.
B-lymphocytes of patients with chronic lymphocytic leukemia differentiate in vitro towards plasma cells upon activation with Pokeweed mitogen (PWM) and Cowan. The level of response is much lower than that of normal cells and so is the helper T-cell function. However, concanavalin A-activated suppressor T-cell function of Ig synthesis is normal. Malignant B-cells have a normal capacity to stimulate Ig synthesis in the mixed lymphocyte cultures, but they respond poorly to an allogeneic stimulus. Thymosin (TFX) causes a marked enhancement of PWM-driven differentiation of malignant B-cells.  相似文献   

12.
E De Nardin  N Tanigaki 《Hybridoma》1985,4(2):125-141
An IgM monoclonal antibody directed against the T-cell E-rosette receptor was obtained by preparing a hybridoma against cells of a human T-cell leukemia line, HPB-ALL. The antibody, named EDN-34B1, reacts exclusively with cells of T-cell lineage, including those of three T-cell leukemia lines. It does not react with cells of B-cell lines, normal B-cells, or monocytes. EDN-34B1 recognizes a single polypeptide of approximately 50,000 molecular weight, is capable of blocking E-rosette formation, and its binding to the target cell can be specifically blocked by monoclonal antibodies 9.6 and OKT-11, both anti-E-receptor antibodies. EDN-34B1 is 100% cytotoxic against normal thymocytes and peripheral T-cells, thus enabling the routine removal of such cells from a mixed lymphocyte population, and kills a higher percentage of normal T-lymphocytes than Ab 9.6, even though immunofluorescence studies have shown that both antibodies bind to the same fraction of PBLs. This phenomenon may be due to the IgM nature of EDN-34B1. Addition of EDN-34B1 and complement to PBLs totally abrogates T-cell functions such as mitogen (PHA) stimulation and response in MLR, while addition of EDN-34B1 alone only affects MLR.  相似文献   

13.
In contrast to pokeweed mitogen (PWM), S. aureus Cowan I (SAC) does not activate suppressor T-cells in cultures of human peripheral blood mononuclear cells, although the SAC induced response leading to the appearance of immunoglobulin secreting cells (ISC) is suppressed by PWM activated suppressor T-cells. Therefore, cultures co-stimulated by SAC and PWM were chosen to find out which stage of the SAC triggered B-cell response is controlled by PWM activated suppressor T-cells. By incorporation of [3H]thymidine and determination of B-cell number in culture it was shown that neither PWM itself nor PWM induced suppressor T-cells interfere with SAC induced B-cell proliferation. The final stages of B-cell maturation were monitored by parallel evaluation of cells producing immunoglobulins (cells with intracytoplasmic immunoglobulins) and secreting them (plaque assay). It was shown that PWM activated suppressor T-cells reduce the number of ISC more effectively than the number of immunoglobulin producing cells, indicating that these two features of differentiated B-lymphocytes may be independently controlled.  相似文献   

14.
15.
《Autoimmunity》2013,46(5):333-347
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16.
Many hypotheses have been proposed to explain the alteration of maternal immune status that allows the fetus to escape rejection. Published data using monoclonal antibodies have stated that there are small variable reductions in circulating T-lymphocytes and little or no change in helper-to-suppressor ratios. Specific decreased levels of helper T-cells have been claimed by other workers. Our laboratory has previously reported alterations in tritiated thymidine uptake (3H-TdR) and HLA antibodies during pregnancy. The present study evaluates total T-cells, lymphocyte T-cell subsets, helper-to-suppressor ratios of T-cells, B-cells, and lymphocyte blast transformation (LBT) throughout pregnancy. These lymphocyte measurements were compared to hormonal changes occurring during pregnancy to determine whether or not hormonal levels have a significant correlation on the maternal immune response during gestation. Data from 100 women revealed no significant alteration of total T-cells or T-cell subsets during pregnancy or after parturition, as measured by monoclonal antibodies. Helper-to-suppressor ratios were within normal limits. B-cells showed a significant decrease (P less than 0.001) during the postpartum period. There was decreased lymphocyte responsiveness to mitogenic stimulation by phytohemagglutinin-P (PHA-P), concanavalin-A (CON-A), and pokeweed mitogen (PWM) in the first, second and third trimesters (P less than 0.01). The mechanisms of fetal protection from maternal immune recognition remain obscure.  相似文献   

17.
Monocyte-T-cell interactions were studied in pokeweed mitogen (PWM)-activated cell cultures. We addressed the question of monocyte changes in PWM-stimulated cultures of T cells and monocytes and found, by flow cytometric analysis, that PWM activation led to a loss of cells with monocyte or macrophage phenotype (CD14, HLA-DR, HLA-DQ) within 48 hr of culture in the presence of T cells (CD4+ T cells), but not in cultures of pure monocytes. Chemiluminescence measurements revealed that phagocytic stimulation of monocytic superoxide release was impaired in PWM-stimulated cultures of monocytes plus T cells, but not in PWM-stimulated cultures of pure monocytes. Furthermore, PWM induced the secretion of interferon-gamma (IFN-gamma) in primary cultures of T cells supplemented with 20% of monocytes, whereas in subsequent secondary cultures of these cells PWM induced IFN-gamma only when monocytes were added. We conclude from these flow cytometric and functional analyses that monocytes are efficiently eliminated from PWM-activated T-cell/monocyte cultures by CD4+ T lymphocytes.  相似文献   

18.
Tetanus toxoid immunization of humans generates circulating B cells which secrete IgG anti-tetanus toxoid antibodies (IgG-Tet) when stimulated in vitro with T cells and pokeweed mitogen (PWM). A unique property of these cells is the inhibition of maturation into antibody-secreting plasma cells following a 1-hr in vitro pulse with tetanus toxoid. Studies were undertaken to determine if different T-cell subsets could modulate the in vitro generated B-cell unresponsive state. The addition of OKT4+/OKT8- cells to antigen-treated B cells resulted in a partial reversal of the antigen-induced inhibition of IgG-Tet synthesis. The addition of OKT4-/OKT8+ cells to the treated B cells caused a suppression of IgG-Tet synthesis comparable to that seen in cultures containing unfractionated T cells. These results indicate that (1) the B-cell unresponsive state generated by antigen treatment is not absolute, (2) the degree of B-cell unresponsiveness results from a balance of suppressor and helper signals, and (3) T-suppressor cells need to be present to induce and maintain the B-cell unresponsive state.  相似文献   

19.
A toddler with common variable hypoimmunoglobulinemia (CVH), inflammatory bowel disease, and recurrent Pneumocystis carinii pneumonia (PCP) on intravenous gammaglobulin (IVIG) replacement was evaluated for a combined cellular immunodeficiency. He had a normal number of circulating T-cells, natural killer (NK) cells, T-cell subset percentages, and his peripheral blood mononuclear (PBM)-derived B-cell number was low. PBM mitogen blastogenesis and mixed lymphocyte reaction (MLR) were normal. MLR activated T-cells expressed class I and II MHC antigens, interleukin 2 (IL-2), and B-cell growth factor (IL-5)-related receptors. The patient's T-cells induced control B-cell maturation with pokeweed mitogen (PWM-PC), and did not suppress PWM-PC production by allogeneic PBM. Bone marrow (BM) CD19+ B-cell number varied between 10 and 44% of all PBM, and the BM B-cell-enriched fraction failed to differentiate to PWM-PC with autologous or allogeneic T-cell help. The NK activity assayed using K562 target cells was deficient, 9.2 x 7.7% (6.9-9.2%) pt, control 35.9 x 35.8% (16.3-67.2% +/- 12.8). In the presence of interferon-alpha, 800 U/ml, the patient's NK activity increased to 17.2 x 14.9% (12.6-17.2%), control 35.9 x 51.0% (36.5-72.3% +/- 12.0). The patient's cell-mediated lympholysis of HLA nonidentical, allogeneic stimulators was normal. Maintaining trough serum IgG levels above 500 mg/dl was required to suppress recurrent PCP. This functional NK deficiency may be relevant to the development of recurrent PCP in IVIG-treated CVH patients.  相似文献   

20.
The contribution of 1 alpha,25-dihydroxyvitamin D3 to the proliferative response of human B- and T-lymphocytes was examined in a serum-free culture, in which B-cells were stimulated with Staphylococcus aureus Cowan I, and T-cells with phytohemagglutinin, respectively. 1 alpha, 25-dihydroxyvitamin D3 inhibited mitogen-induced B-cell proliferation at a dose of 10(-7) M (P less than 0.01). T-cell proliferation was inhibited at the lower dose range between 10(-9) M and 10(-7) M. Thus, although 1 alpha, 25-dihydroxyvitamin D3 acts directly on B-cells, it appears that, under physiological circumstance, 1 alpha, 25-dihydroxyvitamin D3 regulates human B-cell growth indirectly through the effect on T-cells.  相似文献   

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