PubMed Health⌕ Search

Biomedical subjects

J Kaye

Publications and source records attributed to J Kaye.

At least 109 records · Page 6Linked to original sources
PubMed1987

Ability of fixed B-lymphoma cells to present foreign protein antigen fragments and allogenic MHC molecules to a cloned helper-T-cell line.

Cloned, L3T4+ T cells have been shown to respond to foreign protein antigens in the context of self-Ia glycoproteins and to non-self Ia glycoproteins. In the case of responses to foreign proteins, fixed antigen-presenting cells can present antigen fragments, but cannot present native proteins. Whether fixed allogenic cells can stimulate has been controversial. We have examined this question using a dual-reactive cloned helper-T-cell line. We find that conditions of fixation that block the presentation of native antigen to this cloned line, but which allow the presentation of antigen fragments, also allow presentation of allogeneic Ia molecules, leading to stimulation of the cloned line. This study also revealed an occult alloreactivity in the cloned T-cell line, which was expressed by fixed, but not by normal, antigen-presenting B lymphoma cells. All of these stimuli proceeded via the same clonotypic receptor, as determined by blocking with anti-T-cell receptor monoclonal antibody. These data suggest that responses to non-self Ia glycoproteins involve direct recognition of the allogeneic Ia molecules and do not require processing and presentation of these antigens by self Ia molecules.

Animals↗
PubMed1986

Direct interactions between B and T lymphocytes bearing complementary receptors.

A murine cloned Th cell line specific for the antigen conalbumin in the context of self I-A molecules can be activated by low concentrations of soluble antireceptor mAb. By using an antireceptor mAb to shared antigenic determinants on T cell receptors, we have shown that the ability to be activated by soluble antireceptor mAb is an unusual, although not unique, feature of this cloned T cell line. This activation does not involve occult APC, FcR, or interaction between individual cloned T cells, as limiting-dilution analysis shows that individual cells of this clone will grow in the presence of the antireceptor antibody and IL-1 as stimulus. This cloned T cell line is highly immunogenic in vivo, giving rise to antireceptor antibodies that stimulate its growth in both mice and rats. This response is not dependent upon exogenous T cells. Rather, the clone directly interacts with complementary B cells, as shown by the production of mAb in nude mice, and by production of stimulating antireceptor antibodies by purified B cells cultured with cloned Th cells in vitro. Several features of this cloned Th cell line, most especially its ability to be activated, rather than inhibited, by antireceptor antibodies, may account for its striking ability to directly activate B cells bearing complementary receptors. The direct interaction of the cloned Th cell with B cells bearing complementary receptors may serve as a model for receptor-receptor interactions in the generation of both T and B cell repertoires.

Animals↗
PubMed1986

Autocrine growth inhibition of a cloned line of helper T cells.

The growth of T lymphocytes is dependent on the T-cell growth factor interleukin 2 (IL-2), which causes T cells bearing high-affinity receptors for IL-2 to proliferate. Most cloned helper-T-cell lines can be shown to both produce and respond to IL-2; thus, growth of such cells is by an autocrine mechanism. We report that the failure of the cloned murine T-cell line D10.G4.1 to respond to its own IL-2 results from the secretion, by the same cells, of a potent inhibitor of the IL-2-driven T-cell proliferative response. This inhibition can be overcome by increasing the number of IL-2 receptors expressed by the target cell. In the cloned T-cell line producing the inhibitory substance, this increase in IL-2 receptors is driven by the monokine interleukin-1. We propose that this inhibitor of IL-2 responses may play a role in preventing "bystander" activation of T cells by IL-2 released in vivo and could be a potent pharmacologic agent.

Animals↗
PubMed1986

Cell interactions in the immune system: the role of self recognition in the targeting of nonspecific effector molecules by helper T cells.

Helper T cells are activated by cross-linking of their receptors by antigen:Ia complexes on the surface of antigen-presenting cells and B cells. As a result of this cross-linking, the helper T cell releases several lymphokines that in turn affect the Ia-bearing cell with which the helper T cell is in contact. This interaction is cognate when the effect on the target cell is examined, but it operates by a mechanism that is neither antigen specific nor MHC restricted. Whether the cognate nature of this interaction reflects solely the intimate contact of the T cell with the Ia antigen-bearing cell or whether it reflects a receptor-directed focal release of lymphokines remains to be determined. The molecular basis for functional diversity in helper T cells will have to be determined by examining the factors that regulate lymphokine gene expression in such cells, a process that appears to act at several levels.

Animals↗
PubMed1985

Modes of cell:cell communication in the immune system.

Different cell types in the immune system appear to mediate their effects by markedly different means. B lymphocytes couple information for specificity with information for function in a single long-range molecule, antibody. Major histocompatibility complex (MHC)-restricted T cells, which we have analyzed in detail, appear to recognize antigen only on the surface of cells bearing the appropriate MHC gene product. This interaction provokes the T cell to release short-range, non-antigen-specific mediators (lymphokines) that preferentially act on the target cell bearing the antigen and stimulating the T cell. Regulatory T cells appear to make antigen-specific long-range molecules that, like antibody, combine specificity with information for function. However, unlike antibody molecules, these regulatory T cell products display recognition for particular target cells in the form of genetic restrictions. These behaviors are compared to strategies of cell:cell communication in the nervous system.

Animals↗
PubMed1984

The Fab fragment of a directly activating monoclonal antibody that precipitates a disulfide-linked heterodimer from a helper T cell clone blocks activation by either allogeneic Ia or antigen and self-Ia.

We characterize a monoclonal antibody directed against the antigen/Ia receptor of a cloned helper T cell line that induced T cell clone proliferation and T cell clone-dependent B cell proliferation at antibody concentrations as low as 10(-11) M. A Fab fragment of this antibody was not stimulatory, implicating cross-linking of antigen receptors as the primary signal for T cell activation. The Fab fragment inhibited activation of this clone by both allogeneic Ia and antigen plus self-Ia, but not by the nonspecific stimulators concanavalin A and rabbit anti-mouse brain serum. This strongly supports the hypothesis that a single molecule mediates both self-Ia plus antigen and non-self-Ia recognition. This molecule is presumably the disulfide-linked heterodimer comprised of 42,000 mol wt acidic and basic subunits precipitated by this monoclonal antibody. The cell surface and internal precursor forms of this protein are also identified. In addition, the response to allogeneic Ia stimulation was more readily inhibited by the Fab fragment than was the response to antigen plus self-Ia, suggesting that alloreactivity reflects a low affinity interaction with a ligand represented at high frequency on the stimulatory cell.

Animals↗
PubMed1984

The role of B cell surface Ia antigen recognition by T cells in B cell triggering. Analysis of the interaction of cloned helper T cells with normal B cells in differing states of activation and with B cells expressing the xid defect.

Two discrete mechanisms of T-B cell collaboration appear to exist. In cognate recognition, B cell triggering results from a direct recognition of antigen and MHC determinants at the B cell surface. Alternatively, B cells can be triggered by transstimulation, in which the Th cell is activated by an antigen-presenting cell to produce soluble factors which in turn trigger the B cell. This report addresses the question of whether antigen recognition at the B cell surface in association with Ia determinants delivers a signal to the B cell, which is qualitatively different from the signals delivered by the soluble mediators released by the activated Th cell. Previous reports from a number of laboratories suggest that cognate recognition is obligatory for the triggering of small resting B cells and B cells of the Lyb-5- phenotype, whereas enlarged B cell blasts and the Lyb-5+ subset can be triggered solely by soluble mediators. Contrary to these findings, the experiments described here indicate that B cells isolated in different states of activation from normal spleens on the basis of their buoyant density in Percoll density gradients, or unfractionated B cells from mice differing genetically due to the xid defect [Lyb-5- B cells from (CBA/N X BALB/c)F1 male mice], do not discriminate between the two modes of Th cell function. In both stimulation modes, the high density B cells, and the B cells from xid mice made very poor immunoglobulin secretory responses measured in terms of reverse plaque formation on protein A-coupled erythrocytes. When the responses of different density fractions of B cells were compared under conditions where stimulation occurred either directly or indirectly via transstimulation, the following hierarchy of responsiveness in both the proliferative and plaque-forming cell (PFC) responses was observed in the density fractions 60% greater than 65% greater than 70% greater than 75%. The hierarchy was the same in both modes of interaction and the deficiency of the high density, small B cells was far more marked in the PFC assay than in the proliferative assay. We conclude that the initial proliferative response of the resting B cell can be triggered comparably in vitro under conditions of direct or transstimulation. Thus, recognition of B cell surface Ia by Th cells is not obligatory for B cell activation and does not transfer an essential transmembrane signal to the B cell.

Animals↗
PubMed1984

Growth of a cloned helper T cell line induced by a monoclonal antibody specific for the antigen receptor: interleukin 1 is required for the expression of receptors for interleukin 2.

By using as an experimental system the induction of growth of a cloned, antigen:Ia-reactive helper T cell line by an antigen receptor-specific monoclonal antibody, we demonstrated that growth requires two essential co-factors, exogenously produced IL 1 and endogenously produced IL 2. The primary role of the IL 1 is in the expression of receptors on the T cell surface for IL 2, rather than for promoting the synthesis of IL 2. The use of a clone-specific activating monoclonal antibody at nanogram amounts to activate a cloned helper T cell should allow a detailed characterization of T cell activation via antigen receptor cross-linking.

Animals↗
PubMed1983

Both a monoclonal antibody and antisera specific for determinants unique to individual cloned helper T cell lines can substitute for antigen and antigen-presenting cells in the activation of T cells.

Two antisera and a monoclonal antibody raised in BALB.K mice against cloned, major histocompatibility complex (MHC)-restricted, antigen-specific helper T cell lines are described. These antibodies are specific for individual cloned T cell lines and are potent inducers of T cell proliferation. The induction of T cell proliferation by these antibodies requires the presence of an adherent accessory cell. There is no H-2 restriction between this accessory cell and the cloned T cell, nor is this antibody-induced proliferation blocked by a monoclonal anti-Fc receptor antibody. The requirement for an accessory cell, however, is eliminated in the presence of an IL-1- or IL-2-rich supernatant. Thus this system allows the analysis of helper T cell activation with only a single cell type present. Anti-T cell sera also induce T cell-dependent B cell proliferation and immunoglobulin secretion. The induction of T cell-dependent B cell activation by these sera does not require H-2-matched T cells and B cells. The specificity of these antibodies and their ability to stimulate cloned helper T cells in the absence of antigen and antigen-presenting cells strongly suggest that these antibodies are directed against antigen and/or Ia recognition sites on the T cell.

Animals↗
PubMed1983

Subpopulations of B cells distinguished by cell surface expression of Ia antigens. Correlation of Ia and idiotype during activation by cloned Ia-restricted T cells.

We have investigated in vitro the induction of antibody responses to phosphorylcholine (PC) by cloned T helper (Th) cell lines. The cloned Th cells are antigen specific, in this case ovalbumin (OVA), self-Ia recognizing, and induce antibody secretion only if the hapten, PC, is physically linked to the carrier (OVA) molecule. The plaque-forming cell (PFC) response generated in the presence of cloned Th cells is idiotypically diverse with 5-40% of the secreting B cells bearing the TEPC-15 (T15) idiotype. The interaction of the cloned Th cells and unprimed B cells requires recognition of B cell surface Ia glycoproteins for all B cells activated to secrete anti-PC antibody, whether they be T15-bearing or not. More importantly, however, effective interaction between a cloned Th cell and a B cell is determined by the quantity of B cell surface Ia glycoproteins. Our results indicate that quantitative differences in B cell surface Ia antigens are directly related to B cell activation by the cloned Th cell. The high Ia density B cells are most easily activated by cloned Th cells, and these appear to be mainly non-T15-bearing. These data suggest that the failure of cloned Th cells to effectively activate T15-bearing B cells in vitro may be due to the lower relative Ia density of these B cells and therefore to their inability to interact effectively with cloned Ia-recognizing Th cells. These results imply that monoclonal T cells may distinguish between T15-bearing and non-T15-bearing B cells based on their Ia density.

Animals↗
PubMed1983

Voluntary regionalization and associated trends in perinatal care: the Nova Scotia Reproductive Care Program.

The Nova Scotia Reproductive Care Program is a system of voluntary regionalization that involves the 37 hospitals in the province that provide obstetric care to a population of 850,000. Between 1971 and 1980, the perinatal mortality rate in the central tertiary care unit for nonreferred patients fell progressively from 12.5 per 1,000 total births to 5.16. For all cases, including high-risk referrals, this rate has fallen from 12.7 to 7.2. During the same interval, the perinatal mortality rate for the province's seven regional hospitals fell from 18.7 to 12.2, and that for the 28 community hospitals fell from 18.4 to 7.0. Analysis of these reductions by fitted trend lines demonstrates statistical significance. Further analysis demonstrates that, with regionalization of perinatal services, it is possible to reduce the perinatal mortality rate in small community hospitals to levels that approximate those of a sophisticated tertiary care hospital.

Female↗
PubMed1983

Sleep patterns in patients with cancer and patients with cardiac disease.

Thirty cancer out-patients, 28 out-patients with cardiac disease, and 24 controls matched for age, sex, race, religion, and marital status were administered a 38-item questionnaire on sleep habits. Patients with cardiac disease perceived that they had more difficulty falling asleep, awakened earlier than planned, and felt sleepy during the day more often than the other two groups. Patients with cancer differed from controls only in feeling that they had more difficulty staying asleep. The findings demonstrate that while patients with two different chronic diseases have altered sleep patterns, the patterns are disturbed in different ways. This has important implications for therapy as a different approach is needed for the patient who has difficulty falling asleep as compared with the patient who has difficulty staying asleep.

Adult↗
PubMed1983

A cloned, antigen-specific, Ia-restricted Lyt-1+,2- T cell with suppressive activity.

The correlation between cell surface antigen phenotype and function is one of the cornerstones of modern cellular and clinical immunology. It is based on the collective experience of many investigators examining populations of T cells. The availability of cloned lines of T cells now allows us to ask whether all cells sharing cell surface antigen phenotype are functionally equivalent. We have examined a large number of antigen-specific, self-Ia recognizing, cloned Lyt-1+,2- T cell lines for their ability to help B cells proliferate and secrete antibody in response to antigen. All of these lines induced antigen-specific, Ia-restricted B cell proliferation. One line did not induce antibody secretion. This line, indeed suppressed the plaque-forming cell response of B cells helped by any of the other cloned T cell lines tested. Suppression in this system had all the characteristics of classical T cell help, apart from the ultimate outcome. That is, the suppressor cell acted upon the B cell in a manner that was antigen-specific, Ia-restricted, and required hapten-carrier linkage. We interpret our results as supporting the basic paradigm of an association of cell surface antigen phenotype with function, with an important proviso. Not all Ly1, Ia-restricted T cells may be capable of helper function, and some in fact may be suppressive. Experimental conditions favoring the generation of such cells, or disease states in which such cells reside within the Ly1 or T4+ subset, may give rise to disparities between phenotype and function similar to that observed here at the clonal level.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗