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Biomedical subjects

L Chess

Publications and source records attributed to L Chess.

At least 91 records · Page 5Linked to original sources
PubMed1981

Functional analysis of human T cell subsets defined by monoclonal antibodies. II. Collaborative T-T interactions in the generation of TNP-altered-self-reactive cytotoxic T lymphocytes.

In previous reports we have demonstrated that human T cells, responding to soluble and alloantigens, release helper factor(s) that amplify primary in vitro hapten-altered-self-reactive CTL responses. In the present studies, we have employed complement-fixing monoclonal antibodies (OKT4 and OKT8) that recognize functionally distinct human T cell subsets to investigate the role of T-T interaction in the generation of these killer cells. In all experiments, purified OKT4+ responder T cells were deficient in cytotoxic activity, whereas responder populations containing OKT8+ T cells generated substantial cytotoxicity; demonstrating that TNP-altered-self-reactive CTL precursors are contained within the OKT8+ T cell subset. Further, optimal cytotoxic responses were obtained from responder populations containing both OKT4+ and OKT8+ T cells, suggesting that cooperative interaction between these subsets may result in an amplification of killer cell activity. This interpretation was supported by the following observations: (1) the amplifying effect of soluble antigen required the presence of both OKT4+ and OKT8+ responders; (2) during MLC, OKT4+ but not OKT8+ responder T cells generate helper factor(s) that amplify TNP-altered-self-reactive CTL responses; (3) helper factor(s) bypass the requirement for direct OKT4-OKT8 T cell interaction, triggering a CTL response that is proportional to the percentage of OKT8+ T cells present within the responder population. In additional studies, we determined that the TNP-altered-self-reactive effector CTL maintain the OKT3+, OKT4-, OKT8+ surface phenotype displayed by the CTL precursor.

Antibodies↗
PubMed1980

High molecular weight antigens present on human T cells.

A series of eight high molecular weight (140,000-220,000) glycoproteins on human peripheral T cells were recognized by radioimmunoprecipitation with a rabbit antiserum. The pattern of antigens present on each of eight human T cell lines studied was unique, and no line displayed the range of antigens present on peripheral T cells. The pattern of bands on peripheral T cells changed after allogeneic or lectin stimulation. Adsorption/elution experiments with antiserum showed that some of these proteins were antigenically related, and at least three different groups of proteins were present. Two of these groups could be partially distinguished by their ability to bind to ricin or lentil lectin and by their reactivity with two additional rabbit antisera. On some cell lines, it was found that proteins bound by lentil lectin but not ricin were precursors of higher molecular weight material recognized by ricin. Taken together, the data suggest that these proteins may be the products of a multigenic or multiallelic system, probably equivalent to the murine Ly 5 antigens.

Antigens, Surface↗
PubMed1980

MLC-derived human helper factor(s) that promote B cell differentiation: induction, functional characterization, and role of Ia antigens.

Utilizing a PFC assay to quantitate the polyclonal activation of human peripheral blood B lymphocytes, we have investigated the induction and functional activity of MLC-derived human helper factor(s). Our data demonstrate that highly purified responder T cells, but not B or null cells, are required for the elaboration of MLC helper factor(s) that trigger the in vitro differentiation of B lymphocytes into PFC. Helper factor can trigger B cell maturation in the absence of helper T cells, since complement- (C) mediated lysis of the small (less than 5%) fraction of T cells present in anti-F(ab)2 immunoabsorbent column purified B cell population eliminates the PWM induced, but not the helper factor-induced PFC response. Responder T cells required for helper factor production do not bear surface membrane Ia, since alpha p23,30 + C treatment of this population does not affect helper factor generation. In contrast, alpha p23,30 + C treatment of the allogeneic stimulator cell population eliminates helper factor production. Taken together, these results demonstrate that interaction between Ia-bearing stimulator cells and Ia- responder T cells is required for the production of MLC-derived helper factor. In additional experiments, we determined that alpha p23,30, in the absence of C, totally abrogates the PFC response triggered by MLC helper factors. This result suggests an important role for Ia antigens in the functional activity of preformed helper factor molecules.

Antibodies↗
PubMed1980

Hapten-specific human T cell lines. I. Functional analysis with respect to cytotoxic and helper activity.

Human PBL cells, sensitized in vitro to TNP or FITC-modified autologous stimulators, have been successfully grown in long-term culture by using TCGF derived from PHA-activated tonsil cells. Long-term cultures consist almost exclusively of T lymphocytes as defined by the formation of spontaneous rosettes with sheep erythrocytes and C-mediated lysis with heteroantibodies to human T cells (R alpha T H). The majority, but not all of these T cells, bear surface Ia antigens as detected by C-mediated lysis in the presence of alpha p23,30. Functionally, these cultures maintain high levels of hapten-specific cytolytic activity during many weeks of culture. In addition, a number of these T cell lines exhibit hapten specific proliferation when co-cultured with x-irradiated hapten modified autologous cells. During this proliferative response, helper factor(s) are released that trigger B cell differentiation into AFC. Data are presented that demonstrate that helper factor(s) production by T cell line cells is preferentially triggered by autologous, but nt allogeneic stimulator cells, bearing the relevant hapten.

Animals↗
PubMed1980

Functional analysis of human T cell subsets defined by monoclonal antibodies. I. Collaborative T-T interactions in the immunoregulation of B cell differentiation.

T-B and T-T interactions involved in the regulation of PWM-triggered human B cell differentiation were studied in vitro. Functionally distinct human T cell subsets were isolated by C-mediated lysis by using the monoclonal antibodies OKT4 and OKT8. Graded numbers of either untreated or irradiated T cell subsets were added to autologous B cells, and total antibody synthesis was measured after 5 to 6 days of culture by using a highly sensitive reverse hemolytic plaque assay. The data indicate that a) the helper activity that is exclusively contained within the OKT4+ population is radiosensitive. Only at high T/B ratios can this radiosensitivity be overcome; b) the OKT8+ population contains radiosensitive cells important in suppressing B cell differentiation, and c) the suppression induced with OKT8+ cells requires the presence of radiosensitive OKT4+ cells. Thus, OKT8+ cells added to cultures containing B cells and irradiated OKT4+ cells do not suppress the PFC response. Addition of unirradiated OKT4+ cells to these cultures permits reexpression of suppression by OKT8+ cells. It is concluded that two radiosensitive cells, one within the OKT4+ population and the other within the OKT8+ population, collaborate to induce suppression. Possible mechanisms for this suppressive interaction including induction of suppressor precursor cells within the OKT4+ population or inhibition of OKT4+ helper cells by OKT8+ cells are discussed.

Antibodies↗
PubMed1979

Participation of monocyte-macrophages and lymphocytes in the production of a factor that stimulates collagenase and prostaglandin release by rheumatoid synovial cells.

Cultured mononuclear cells from human peripheral blood produce a soluble factor (MCF) that stimulates collagenase and prostaglandin E2 (PGE2) release by cultured rheumatoid synovial cells up to several hundred fold. These target rheumatoid synovial cells lack conventional macrophage markers. To determine which mononuclear cells are the source of MCF, purified populations of monocyte-macrophages, thymus-derived (T) lymphocytes, and bone marrow-derived (B) lymphocytes were prepared. The monocyte-macrophages alone produced levels of MCF that were proportional to cell density but unaffected by phytohemagglutinin or pokeweed mitogen. No detectable collagenase activity was produced by the cultured monocyte-macrophages or lymphocytes. Purified T lymphocytes produced levels of MCF approximately or equal to 1--3% those of purified monocyte-macrophages in the presence or absence of the above lectins. Purified T lymphocytes modulated the production of MCF by the monocyte-macrophages, however, in a manner dependent upon relative cell densities and the presence of lectins. For example, at optimal ratios of T lymphocytes: monocyte-macrophages, MCF production was markedly stimulated by pokeweed mitogen. Thus, interactions of T lymphocytes and monocyte-macrophages could be important in determining levels of MCF, which regulate collagenase and PGE2 production by target synovial cells in inflammatory arthritis.

Arthritis, Rheumatoid↗
PubMed1979

The induction of TNP-altered, self-reactive human cytotoxic T cells by soluble factors: the role of Ia antigens.

This report demonstrates that human peripheral blood T lymphocytes, triggered by allogeneic cells or soluble antigens, elaborate helper factor(s) that promotes the in vitro differentiation of TNP altered-self reactive human CTL. Helper factor(s) alone is not sufficient for the generation of these killer cells, but requires the presence of TNP-derivatized autologous stimulators during sensitization. Additional experiments were performed with antisera to a human Ia-like antigen, p23, 30. These studies indicate that human Ia-like antigens play an important role in both the induction of helper factor(s) and in the functional activity of preformed helper factor(s) molecules.

Cytotoxicity, Immunologic↗
PubMed1978

Normal erythropoietic helper T cells in congenital hypoplastic (Diamond-Blackfan) anemia.

To examine the erythropoietic function of T and null cells in congenital hypoplastic (Diamond-Blackfan) anemia, we fractionated the peripheral blood of three normal subjects and three affected patients into subclasses of null, T and B cells. Mixtures of these cells were co-cultured in plasma clots in the presence of erythropoietin. Erythroid colonies grew in cultures of normal null cells if either normal or patient T cells were co-cultured with them. Null cells of patients with hypoplastic anemia did not produce erythroid colonies under any culture conditions. We conclude that in this disorder, T cells function normally as helper cells in erythropoiesis and do not suppress colony formation, whereas the erythroid progenitor cells in the peripheral blood null-cell fractions are deficient in either number of function.

Adolescent↗
PubMed1978

Human erythroid burst-forming unit: T-cell requirement for proliferation in vitro.

Human mononuclear leukocytes were fractionated into populations of null, T and B cells by immunoabsorbent column chromatography followed by E-rosette formation and purification of T cells by differential centrifugation and osmotic lysis. The unfractionated and fractionated cell populations were first separately cultured for 14 days in plasma clots in the presence of two international units erythropoietin. Typical erythroid burst-forming unit (BFU-E)-derived colonies grew in the unfractionated cell cultures but not from T- or B-cell cultures. BFU-E colonies grew in null cell cultures but most of the colonies were small and variably hemoglobinized with less than three subcolonies. When intact T cells were added to null cells and cocultured, many typical large BFU-E colonies with more than 10 well homogenized subcolonies appeared. Increasing numbers of large BFU-E colonies in null cell cultures were induced by stepwise addition of T cells but not by the addition of B cells. A conditioned medium in which T cells had been induced to divide by tetanus toxoid substituted for intact T cells in this T-cell-dependent BFU-E colony formation observed in null cells. These findings demonstrate that the BFU-E, a committeded erythroid stem cell, resides in the null cell fraction of peripheral blood, but its proliferative capacity and differentiation in vitro requires a soluble product of T cells. Such experiments now permit a new approach to the assessment of various disorders of erythropoiesis. Erythroid hypoplasia in a particular case may be due to dysfunction of the committed precursor cell or to a failure of a helper effect induced by T cells.

B-Lymphocytes↗
PubMed1978

Antibody-dependent cellular cytotoxicity by allosensitized human T cells.

Peripheral human T cells, isolated by sheep erythrocyte-rosette formation and density centrifugation, were highly cytotoxic to both Ab-coated autologous lymphocytes and antibody (Ab)-coated chicken erythrocytes when stimulated in mixed lymphocyte culture, but were not lytic when freshly purified, or when unstimulated in 6-day culture. Allosensitized T cells were shown to effect this activity by a specific effector-target cell interaction dependent on Ab, as indicated by: (a) induction of killing by Ab to target cells not lysed in the absence of Ab. (b) inhibition of Ab-dependent killing by aggregated Ig. The mechanism by which allosensitized T cells effect antibody-dependent cellular cytotoxicity is discussed.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1978

Isolation and characterization of naturally occurring subclasses of human peripheral blood T cells with regulatory functions.

By utilizing naturally occurring autoimmune antibodies from patients with juvenile rheumatoid arthritis, we have isolated and functionally characterized two unique subpopulations of T cells. JRA+ T cells, i.e., those identified by sera from these patients, react poorly in response to allogeneic cells, respond to Con A but not PHA, and do not help in the synthesis and secretion of Ig by B cells. In contrast, JRA- T cells, i.e., those not identified by sera from these patients, respond very well to allogeneic cells, proliferate well in response to PHA but not Con A, and more interestingly, can greatly enhance the secretion of Ig by B cells.

Antigens↗
PubMed1978

Replication of herpes simplex virus and cytomegalovirus in human leukocytes.

Human peripheral blood leukocytes, lymphocyte subpopulations, and hemic cell lines were examined for their ability to supprot HSV and CMV replication. Mitogen-stimulated mononuclear leukocytes, B lymphocytes, and T lymphcytes supported the replication of HSV to high titers over 3 to 5 days of infection. HSV replicated in unstimulated mononuclear leukocyte cultures of one of five donors, and to a limited degree in untreated B lymphocytes of three of five donors; HSV replication was not detected in unstimulated T lymphocytes (five donors). There was no evidence of enhanced uptake of 3H-thymidine in the untreated donor cells that replicated HSV. CMV replication was not detected during 9 to 10 days of infection in untreated or mitogen-treated mononuclear leukocytes and lymphocyte subpopulations from the same adult donors or in neonatal cord blood leukocytes. The ability of the cells to support HSV or CMV replication did not correlate with the presence of specific antiviral antibodies in the donor serum. HSV replication in B, T, and myeloid cell lines to high titers over 5 days of infection, whereas CMV failed to replicate in any of the hemic cell lines. A persistent HSV infection has been established in a T cell line (CEM) with high titers of infectious virus being produced concurrently with growth of the cells over the first 11 weeks of infection.

Antibodies, Viral↗
PubMed1978

Characterization of a unique cell line (LAZ 221) from human acute lymphocytic ("null" cell) leukemia.

A unique human cell line designated LAZ 221 has been established from the peripheral blood of a patient with acute lymphocytic leukemia of the "null" cell type. The cell line does not possess the Epstein-Barr virus nuclear antigen and has a karyotype of 45,XX,-9,-12,+(9q12q). Both the established cell line and the patient's uncultured blast cells share the same phenotypic markers. They both lack T-cell markers. They fail to form sheep erythrocyte rosettes and do not react with T-cell-specific antisera (TH1-, HTL-), nor do they possess B-cell markers. They do not form rosettes with erythrocytes sensitized with complement, and they are surface immunoglobulin negative. However, they do possess an HLA-D-related glycoprotein complex of 23,000 to 30,000 daltons, an la-like antigen. Thus, LAZ 221 shares the phenotype of the patient's uncultured blasts and is a cell line representative of about 75% of all human acute lymphocytic leukemias. In this respect it differs from previously described human hematopoietic cell lines.

Adult↗
PubMed1978

Suppression of in vitro Epstein-Barr virus infection: a new role for adult human T-lymphocytes.

In vitro EBV infection of lymphocytes from different sources indicated that B-cells of adult peripheral or fetal cord blood transform with equal efficiency whether assayed by DNA synthesis induction or immortalization. Unfractionated adult lymphocytes transformed much less efficiently than those from fetal cord blood. This effect was due to the suppression of B-cell proliferation by adult T-lymphocytes.

Adult↗
PubMed1978

Cell-mediated lympholysis of trinitrophenyl-derivatized autologous human cells: in vitro triggering by nonspecific signals.

This report describes the primary in vitro generation of human CTL that lyse TNP-derivatized autologous cells. Although in the majority of these studies, a direct cytotoxic response to the TNP-modified autologous stimulators was not achieved, in all experiments the addition of either allogeneic cells or soluble antigen triggered the generation of killer cells which destroy TNP-modified, but not unaltered, autologous targets. Fractionation of responder lymphocyte populations demonstrated that the cytotoxic activity was mediated by T cells. Killer cell specificity was tested by assaying for cytotoxicity to a variety of targets, and by blocking the cytolysis of TNP-altered autologous targets with various populations of nonradiolabeled cells. Results indicated that these CTL were cytotoxic for TNP-modified autologous cells but not unaltered autologous or TNP-modified allogeneic targets. The capacity of soluble antigen and alloantigens to facilitate the in vitro generation of altered-self reactive human CTL is not an isolated phenomenon. This "helper" effect has now been observed for the cytotoxic response to chemically modified autologous cells and MHC identical human leukemic blasts. It is possible that in vivo, similar responses to nonspecific antigenic stimuli may play a role in the maintenance of immune surveillance.

Antigens↗