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J Quintans

Publications and source records attributed to J Quintans.

35 records · Page 2Linked to original sources
PubMed1990

The regulatory role of human helper T-cell clones on antithyroid antibody production by peripheral B-cells.

The helper effects of thyroid antigen-specific T-cell clones (TCC) on antibody production by peripheral B-cells were studied and compared with similar effects of self major histocompatibility complex II (MHC-II)-reactive TCC as well as uncloned CD4+ cells. Ten TCC were derived from thyroid tissue or peripheral blood mononuclear cells (PBMC) in patients with Graves' disease. Uncloned CD4+ cells were also obtained from PBMC in patients with autoimmune thyroid disease. All TCC were CD3+/CD4+. B-Cells from patients with mainly high serum levels of microsomal antibodies (McAb) were cultured alone and with either TCC or uncloned CD4+ cells in the presence or absence of thyroid antigens [microsomal antigen/thyroid peroxidase (McAg/TPO) and thyroglobulin (Tg)] or pokeweed mitogen (PWM). Total immunoglobulin G (IgG) and specific thyroid antibodies were measured by enzyme-linked immunosorbent assay. Self MHC-II-reactive TCC induced B-cell production of total IgG and even McAb independent of antigens or PWM. Specific TCC required thyroid antigens to induce antibodies. The optimal McAg/TPO or Tg concentration was 10 ng/mL for total IgG production and 1 ng/mL McAg/TPO for McAb synthesis. The addition of PWM did not affect McAb production, but enhanced total IgG synthesis by B-cells under the influence of some specific TCC. Uncloned CD4+ cells induced both total IgG and McAb synthesis in the presence of PWM. With thyroid antigens, uncloned CD4+ cells induced total IgG synthesis at levels comparable to those of specific TCC, but induced smaller quantities of McAb in the presence of McAg/TPO. Our antigen-specific TCC could, therefore, stimulate specific B-cells to produce thyroid antibodies in vitro. Self MHC-II-reactive TCC could also induce specific antibodies by B-cells. Both self MHC-II-reactive CD4+ cells and antigen-specific CD4 cells may play an important role in the pathogenesis and/or perpetuation of autoimmune thyroid disease.

Antibodies↗
PubMed1989

Accessory cell function of Th2 clones.

We have investigated the ability of T helper clones to serve as accessory cells and in the presence of mitogen activate freshly-isolated, splenic T cells. In this type of costimulatory assay, the Th cells that secrete IL-4 but not the Th cells that secrete IL-2 function as AC to induce T cell proliferation in the presence of various T cell mitogens (Con A, anti-CD3 mAb, anti-TCR mAb, and anti-Thy-1 mAb). The signal provided by the accessory Th2 cells occurred independently of MHC restriction, and the analysis of dose-response curves showed the involvement of a single stimulator cell. CD4, as well as CD8 expressing splenic T cells were induced to proliferate by the Th2 clones and mitogen, but mAb specific for CD4 or CD8 failed to affect the response. These findings indicate that cloned Th2 cells functioned as accessory cells and induced naive T cells to proliferate in the presence of mitogen.

Animals↗
PubMed1989

Production of IL-2 and IFN by TH2 clones.

We have studied the production of IL-2, IL-4 and IFN-gamma by a panel of CD4+ clones produced in our laboratory. The clones were classified as TH1 and TH2 because of their ability to secrete IL-2 or IL-4, respectively, following stimulation with APC + Ag and by their characteristic proliferative responses to exogenous IL-2 or IL-4. Some of the TH2 clones, all of which happened to be autoreactive, produced IL-2 and one of these, as well as one antigen-reactive TH2 clone, also secreted IFN-gamma following stimulation with immobilized anti-CD3 mAb. IL-2 production by TH2 cells required higher concentrations of anti-CD3 mAb than IL-4 production. Thus, the TH2 clones seem to be heterogeneous. We designate the IL-2/IL-4 secretors as TH2B and those making IL-4 as TH2A clones.

Animals↗
PubMed1989

The role of autoreactive T-cell lines in the restoration of the immune response to sheep red blood cells in C57Bl/6-lpr/lpr mice.

Although autoimmune-prone mice bearing the lymphoproliferation (lpr) gene have polyclonally activated B cells and high serum titers of autoantibodies, they mount poor immune responses to exogenous antigens. In addition, they exhibit very low or nonexistent autologous mixed lymphocyte responses. Previous studies have shown that autoreactive T-cell clones have immunoregulatory properties: they can help suppress, or contrasuppress an immune response. Here we show that two autoreactive T-cell lines, GB4 and B1H1, can restore the defective response of C57Bl/6-lpr/lpr mice to the antigen sheep red blood cells. This restoration is antigen-dependent and requires the presence of other T cells.

Animals↗
PubMed1989

T helper 2 (Th2) but not Th1 clones co-stimulate resting T cells in the presence of anti-CD3 monoclonal antibody.

We have investigated the effects of monoclonal antibody (mAb) to the CD3 epsilon protein on interactions between small, resting T cells and antigen-specific T helper clones. Highly purified, splenic T cells lacking identifiable accessory cells do not proliferate in a thymidine uptake assay to anti-CD3 mAb, Con A, rIL-2, rIL-4, or irradiated T helper clones (both Th1 and Th2). However, the responding T cells proliferate significantly to the combined stimulus of Th2 clones and anti-CD3 antibody. Only the Th2, not the Th1, subpopulation of T helper cells has the ability to induce a T cell response. The Th2 cell-dependent activation of small resting T cells does not require the external cross-linkage of the anti-CD3 mAb via Fc receptor expressing cells or the secretion of lymphokines from the Th2 helper clones, but it is inhibitable by anti-LFA 1 antibody. Thus, Th2 clones provide a co-stimulatory signal which in conjunction with anti-CD3 mAb causes resting T cell proliferation in the absence of conventional accessory cells.

Animals↗
PubMed1988

Antigenicity of passively acquired major histocompatibility antigens on T cells.

T cell blasts and lines passively acquire MHC molecules in vitro. To determine the role of these molecules in immunoregulatory reactions, we examined whether T cell lines grown on irradiated F1 spleen cells were able to supply allogeneic MHC antigens for the stimulation of T cell proliferation. Immunofluorescence analysis demonstrates that autoreactive T cell lines grown with irradiated F1 spleen cells acquire allogeneic class II molecules and subsequently lose the MHC molecules within 4 days of coculture with syngeneic cells. The proliferative response of (H-2k x H-2d)F1T cells stimulated by a T cell line grown on (H-2k x H-2d)F1 cells is inhibited by the addition of hybridoma-culture supernatants containing anti-IAd as well as anti-IEk antibodies. The proliferation of the F1 T cells to the T cell line grown on H-2k spleen cells is only affected by supernatants containing anti-IEk antibodies. To investigate the role of acquired class I MHC antigens, we examined their ability to serve as antigens for cytotoxic cells. Anti-H-2k cytotoxic T cells are generated when H-2b T cells are cultured with an H-2b-derived T cell line, only if the line has been grown on (H-2k x H-2b)F1 cells. An H-2b-derived T cell line exposed to (H-2k x H-2b)F1 cells can be lysed by anti-H-2k cytotoxic T cells from a primary MLR. Similarly, an H-2k anti-H-2b cytotoxic T cell clone will kill an H-2k-derived T cell clone grown on (H-2k x H-2b)F1 spleen cells. These results demonstrate that passively acquired class I molecules can stimulate the generation of cytotoxic T cells that lyse cells expressing the class I antigens and that passively acquired class I molecules expressed on T cells serve as the target for cytotoxic T cells.

Animals↗
PubMed1988

Microsomal antigen-reactive lymphocyte lines and clones derived from thyroid tissue of patients with Graves' disease.

Thyroid mononuclear cells (TMC) were maintained in long term cocultures with thyroid fibroblasts and thyroid epithelial cells from patients with Graves' disease, using medium supplemented with thyroid microsomal antigen (McAg) and IL-2. The TMC consisted predominantly of T4+ (CD4+, helper) and, to a lesser extent, T8+ (CD8+, cytotoxic/suppressor) lymphocytes, with a small number of macrophages and natural killer cells. The average T4+ to T8+ ratio was 3.2. From these cultures we obtained thyroid T cell lines and clones reactive to thyroid antigens. T Cell lines were tested in a microproliferation assay using thyroglobulin (Tg), McAg, tetanus toxoid, and IL-2. Of 14 lines from 6 patients, 2 proliferated in response to McAg when TMC plus thyroid fibroblasts were used as antigen-presenting cells. Clones of thyroid lymphocytes were obtained by culturing cells at limiting dilution with IL-2, McAg, and different types of autologous accessory cells. Peripheral blood mononuclear cells plus skin fibroblasts provided the best source of accessory cells, allowing near 100% cloning efficiency. Of 26 clones tested, 6 recognized McAg, 2 were Tg reactive, and 3 were autoreactive. All phenotyped clones were of the T4+ phenotype. Our method results in production of thyroid T cell lines and clones. The fibroblasts probably provided growth factors and/or collaborated with peripheral blood mononuclear cells as antigen-presenting cells. These lines and clones from patients with Graves' disease were predominantly helper T cells, in contrast to the previously demonstrated cytotoxic/suppressor cell predominance in cells from patients with Hashimoto's thyroiditis. This difference in cell function may help explain the differing clinical courses of these two closely related autoimmune thyroid diseases. The availability of long term microsomal antigen-specific T cell clones should allow careful analysis of the role these cells play in thyroid autoimmunity.

Antigens↗
PubMed1988

B-cell transplants to immunodeficient xid neonates do not imprint their helper T cells.

A great variety of Igh-restricted immunoregulatory phenomena have been described in responses to both haptens and carriers. The investigation of Igh-dependent T-cell functions is of considerable interest because it relates to issues such as the interdependence of the T- and B-cell networks, isotope- and idiotype-specific help, the role of Igh-linked products in the generation of the helper and cytolytic T-cell repertoires and Igh-linked effects on cell interactions among helper and suppressor cells. Helper T cells have been shown to be critically susceptible to B cell-mediated education and it is generally assumed that T cells become imprinted by B-cell idiotypes during development. It occurred to us that xid immunodeficient neonates, which lack T15+ B cells and T15 antibodies, might provide a suitable host to investigate the B-cell dependent imprinting of T cells providing help in T15+ anti-PC responses. We designed our experiments to test whether or not T15 deficient xid mice could be used as recipients of normal B cells capable of imprinting the host's helper cells. The results of our experiments demonstrate that unirradiated xid neonates are readily engrafted with normal B cells from both neonatal and adult donors. The transplanted B cells reconstitute anti-PC and anti TNP-FICOLL PFC responses in the xid hosts. However, the early engraftment of T15+ B cells in xid mice did not cause a detectable imprinting of their helper T cells, i.e., we could not detect any biases in the preference of carrier-/primed cells from reconstituted mice for primary or secondary T15+ or T15- B cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

IFN-gamma is not an essential mediator of murine antibody responses in vitro.

We have used purified murine gamma-interferon (Mu IFN-gamma) and anti-Mu IFN-gamma monoclonal antibody to study the participation of gamma-interferon (IFN-gamma) in in vitro plaque-forming cell (PFC) responses to antigen. We have studied several supernatants with T-cell replacing factor (TRF) activity as well as helper T-cell dependent anti-sheep red blood cells (SRBC) PFC responses. Our findings demonstrate that neither TRF- nor T-cell mediated responses are critically dependent upon IFN-gamma.

Animals↗
PubMed1987

Alterations of idiotypic profiles: the cellular basis of T15 dominance in BALB/c mice.

Phosphorylcholine (PC) is a component of cell walls and membranes from a variety of widely distributed microorganisms. It is highly immunogenic in mice and most murine strains have circulating anti-PC antibodies which are known to confer protection against certain bacterial infections. BALB/c mice offer a striking example of a high responsiveness to PC, a propensity to generate PC-binding myelomas, and a great restriction of idiotype expression in anti-PC antibodies; in fact, most BALB/c anti-PC IgM antibodies express the T15 idiotype marker. Although it has been suspected that T15 dominance is somewhat related to the continuous antigenic load presented by microorganismal flora found in conventional mice, a complete experimental account of how antigenic selection brings about such extreme idiotypic dominance is not yet available. In the studies presented below, we investigated the role played by the host environment, T cells, and antigen in affecting the generation of the anti-PC T15 idiotype profile in lethally irradiated adoptive hosts reconstituted with syngeneic neonatal liver cells. The results presented herein indicate that the transfer of mature carrier-primed T cells with neonatal liver cells does not influence the generation of the T15 idiotype profile. We also demonstrated that anti-T15 idiotype suppressed mice, used as lethally irradiated hosts of immature immunocompetent cells, allow an increased rate of reconstitution of the anti-PC response when compared to nonsuppressed hosts. Since the administration of a T15+ anti-PC antibody inhibits both reconstitution and idiotype expansion, we conclude that T15+ B cells do not self-promote themselves. In contrast, we observed that exposure of adoptive hosts to PC antigens can enhance the anti-PC response and alter the idiotypic profile in favor of T15-bearing clones. The failure of T15 idiotype and the success of PC antigens in promoting T15 dominance led us to search for an "antigen inside" which might play a role in the ontogeny of T15 expression. To this end, we produced isologous anti-T15 hybridomas and selected one BH8 binding IgM hybridoma, 15B1, as a potential carrier of an internal image of PC. In vivo tests involving the administration of this antibody to irradiated adoptive hosts immediately prior to the transfer of neonatal liver cells indicate that T15 expression in adoptive transfer can be enhanced by this antibody. Finally, we discuss a model to account for the generation of T15 dominance in normal adult BALB/c mice and its loss in adult BALB/c mice used as adoptive hosts for syngeneic immature immunocompetent cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1985

Stimulation of lymphoid cell proliferation by Mycoplasma orale, a common cell culture contaminant.

Mycoplasma orale, maintained as a contaminant of a mouse hybrid cell line, induces an intense proliferation in short-term culture of lymphoid cells of inbred mice. Cell division induced by the contaminated cell culture fluid reaches a maximum on day four and declines rapidly thereafter. Culture fluids from hybrid cells freed of contamination do not cause proliferation. Cells from the spleen, bone marrow, and thymus of each of several strains of inbred mice, including xid CBA/N, poorly responsive to lipopolysaccharide, are stimulated by the mitogen, as are cells from BALB/c nude mice. The characteristics of the stimulatory effect are analogous in several important aspects to those of naturally occurring T cell-derived growth factors. In the absence of detectable numbers of T cells, both small and large B lymphocytes undergo mitosis in the presence of contaminated cell culture fluid, and B cells stimulated to divide by lipopolysaccharide are sustained for further rounds of replication by M. orale-containing cell culture fluid. The fluid also augments the stimulatory effect on thymocytes of suboptimum concentrations of phytohemagglutinin mimicking the effect of interleukin-1. Unlike with most naturally occurring lymphoid cell mitogens, however, the dividing cells do not go on to immunoglobulin secretion.

Animals↗
PubMed1982

Alloreactive cloned T cell lines. VI. Multiple lymphokine activities secreted by helper and cytolytic cloned T lymphocytes.

Culture supernatants generated by alloantigenic or lectin stimulation of a cloned helper T lymphocyte, designated L2, contain interleukin 2 (IL 2), granulocyte/macrophage colony-stimulating factor (CSF), B cell stimulating factor (BCSF), macrophage (Ia+)-recruiting factor (MIRF), (Ia+)-inducing activity, gamma-interferon, Fc receptor-enhancing activity, macrophage migration inhibitory factor (MIF), macrophage activation factor (MAF), interleukin 3 (IL 3), and a factor responsible for prolonging the synthesis and secretion of the fourth and second components of complement by guinea pig peritoneal macrophages. Erythropoietin was not detected. A spontaneously arising variant of L2, designated L2V, produces much lower quantities of macrophage-stimulating activities, IL 2, and interferon. However, when compared to L2, L2V produces much higher levels of BCSF, equivalent amounts of IL 3, and slightly smaller amounts of CSF. Unlike L2V, a cytolytic clone, designated L3, secretes lymphokines that primarily affect macrophage function. The time course of lymphokine production by L2 cells indicates that for the six lymphokine activities studied there are three different times at which maximal or near maximal levels are reached, as follows: 1) IL 2, 12 to 24 hr; 2) IL 3 and CSF, 24 to 48 hr; and 3) (Ia+)-inducing activity, MAF, and interferon, 48 hr or later. Only IL 2 activity disappears during the 8-day culture cycle. The time course data and the differential production of activities by the three types of lymphocyte clones suggest that at least four terminal effector lymphokine molecules account for the ten biologic activities tested.

Animals↗
PubMed1981

Alloreactive cloned T cell lines. II. Polyclonal stimulation of B cells by a cloned helper T cell line.

A cloned helper T cell line, L2, has been derived that promotes the proliferation of cytolytic T cells with the concomitant expression of cytolytic activity. L2 helper cells also cause a polyclonal stimulation of B cells in the absence of antigen, as measured by the number of total plaque-forming cells (PFC) as well as those generated toward TNP or SRBC. The L2 helper cell function is dependent on cell number, is radioresistant, and is mediated via soluble factor(s). Maximum levels of PFC were generally observed after 4 days of culture, with IgM-secreting B cells being predominantly induced in these cultures. Both the proliferation of and stimulation by L2 helper cells are activated by Misa determinants. F1 progeny from a mating of CBA/N and DBA/2 (Mlsa) that did not bear Mlsa (NDF1) were nonstimulatory, whereas those F1 animals bearing Mlsa (DNF1) induced L2 helper-cell proliferation and function. L2 helper-cell recognition of Mlsa determinants present on the responding B cell surface was not required for polyclonal helper-dependent stimulation in vitro. L2 cells stimulated polyclonal antibody secretion in syngeneic as well as allogeneic B cells. Since Mls antigens are not expressed on T cells, these results indicate that regulatory T cell circuits are initiated by non-T cells, possibly B cells.

Animals↗
PubMed1981

Alloreactive cloned T cell lines. V. Differential kinetics of IL 2, CSF, and BCSF release by a cloned T amplifier cell and its variant.

A noncytolytic, Thy-1+, MIs-responsive cloned T amplifier cell, designated L2, derived from secondary C57BL/6 anti-DBA/2 mixed leukocyte culture was found to produce IL 2 (Interleukin 2), granulocyte/macrophage colony-stimulating factor (CSF), and a polyclonal B cell-stimulating factor (BCSF) after alloantigenic stimulation. IL 2 activity was present transiently, with maximal levels observed 12 to 24 hr after exposure to alloantigen. Only trace amounts were present 96 hr after initiation of culture. CSF and BCSF activities were present at high levels by 24 hr and remained elevated throughout an 8-day culture period. Further evidence that the lymphokine(s) having IL 2 activity is different from those having CSF and BCSF activities was provided by L2V, a variant of L2 that did not produce IL 2. The time course of CSF and BCSF production by L2V after stimulation with alloantigen was similar to that found with L2, although IL 2 activity was not detected at any time. Since the release of lymphokines from both L2 and L2V cells could be induced by Con A in the absence of stimulating alloantigen, it is likely that the biologically active factors were produced by the cloned T cell.

Animals↗
PubMed1978

Clonal dominance: loss and restoration in adoptive transfer.

An adoptive transfer system was used to study the mechanism responsible for clonal dominance of the anti-phosphorylcholine response in BALB/c mice. The adult spleen contains phosphorylcholine-specific precursor cells that are capable of developing into antibody-producing cells after transfer into lethally irradiated animals. The neonatal liver of the BALB/c mouse lacks precursor cells specific for phosphorylcholine but contains immature cells that differentiate into specific precursors during the normal course of ontogeny. The transfer of fetal or neonatal liver cells into lethally irradiated recipients prevents the appearance of the dominant H8 clone which constitutes the majority of the clones responding to phosphorylcholine in adult BALB/c mice. However, if these cells are transferred into neonatally suppressed recipients that lack the H8 idiotype, dominance of the H8 clone can develop. The conversion of the committed immature progenitor cell into a responsive B lymphocyte precursor is a regulated event. Regulation at the level of progenitor cells determines the eventual clonal profile of the immune response to phosphorylcholine. It is suggested that selection of the dominant clone occurs at this level.

Animals↗