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Y Thomas

Publications and source records attributed to Y Thomas.

70 records · Page 4Linked to original sources
PubMed1982

Further dissection of the functional heterogeneity within the OKT4+ and OKT8+ human T cell subsets.

Previous studies have suggested functional heterogeneity within the OKT4+ and the OKT8+ populations. For example, after activation the OKT4+ population contains not only helper cells but also cells capable of suppressing B cell differentiation. Previous studies also indicate that the reciprocal T cell population, OKT8+, does not provide helper activity but contains cytotoxic effector cells and radiosensitive cells important in the suppression of B cell differentiation. Using a new differentiation antigen, OKT17, which recognizes a surface antigen present on the majority of resting normal peripheral T lymphocytes but is present only on a subset of OKT4+ cells after activation, evidence was obtained that two functionally mature subsets can be distinguished within the OKT4+ population itself: OKT4+17+ radiosensitive suppressor cells and OKT4+17- radiosensitive helper cells. Recently, another monoclonal antibody, OKT20, has been described which is present on a small percentage of resting lymphocytes but is expressed in varying proportions on activated T cells. Functional analysis of normal resting human T lymphocytes demonstrated that the OKT20-depleted T cell subset was able to generate cytotoxic cells and to suppress antibody production to the same extent as did OKT8+ cells. On the other hand, when unselected T lymphocytes were cultured for six days in a mixed lymphocyte reaction and then depleted of OKT20 reactive cells, the cytotoxic effector T cells were eliminated. In contrast, OKT20-depleted T cells after identical activation were still able to suppress antibody production. These data provide evidence that following activation of OKT8+ cells, the OKT20 differentiation antigen becomes selectively expressed on cytotoxic effectors but not on suppressor cells.

Antibodies, Monoclonal↗
PubMed1982

Functional analysis of human T cell subsets defined by monoclonal antibodies. V. Suppressor cells within the activated OKT4+ population belong to a distinct subset.

In the present report, we characterize a monoclonal antibody directed at a surface differentiation antigen on human T cells. The monoclonal antibody, OKT17, recognizes a cell surface antigen present on the majority of resting normal peripheral T cells. In contrast, OKT17 is unreactive with normal B cells, B cell lines, T cell lines, or SIg+ CLL. Interestingly, after activation, the antigen recognized by OKT17 is lost from a subset of OKT4+ cells. We took advantage of this finding to explore further the functional heterogeneity within activated OKT4+ cells. Evidence was obtained that the PWM-activated OKT4+ subset remaining after depletion of OKT17-reactive T cells (OKT4+ 17-) contains radiosensitive helperr cells but is devoid of suppressor cells. In contrast, the activated OKT4+ 17+ population contains potent radiosensitive suppressor cells as well as radioresistant helpe cells. Taken together, these studies suggest that the OKT17 monoclonal antibody can differentiate two functionally mature, activated OKT4+ human T cells: OKT4+ OKT17+ radiosensitive suppressor cells and OKT4+ 17- radiosensitive helper cells.

Antibodies, Monoclonal↗
PubMed1981

Generation of functional human T cell hybrids.

Human T cell hybrids were generated by fusing lectin-activated normal and leukemic human T cells with an aminopterin-sensitive human T cell line. This mutant cell line, designated CEM-T15, was derived from the human T cell line CEM after chemical mutagenesis with ethane methylsulfonate and subsequent culture in medium containing 6-thioguanine. After polyethylene glycol-induced fusion, the cells were cultured in hypoxanthine-aminopterin-thymidine selective medium. More than 5 wk after fusion, evidence for successful hybridization was obtained by three independent criteria: (a) The majority of the cultures contained cells expressing the OKT3 surface antigen: this antigen is expressed on normal T cells but not on CEM-T15 cells. (b) Most of the cultures contained polyploid cells. (c) Some of the cultures provided helper activity in the generation of antibody-forming cells. This functional activity is absent from the CEM-T15 parental cell line. Evidence for functional stability of the hybrids greater than 20 wk after fusion was provided by several clones that not only continue growing exponentially but also maintain expression of OKT3 surface antigen and high levels of helper function. These T cell hybrids constructed using antigen-specific human T cells should be of considerable importance in further studies of the immunobiology of human T cells.

Aminopterin↗
PubMed1981

Functional analysis of human T cell subsets defined by monoclonal antibodies. IV. Induction of suppressor cells within the OKT4+ population.

In this report, we explored the functional heterogeneity within the OKT4+ subset of human T cells. Evidence was obtained that although in vitro pokeweed mitogen-activated OKT4+ cells can function as radioresistant helper cells, these activated OKT4+ cells could also exert potent feedback suppression. Despite the induction of suppressor cells after pokeweed mitogen activation, the OKT4+ population maintains its original OKT3+, OKT4+, nd OKT8- surface phenotype. The suppressor cells contained within the activated OKT4+ population were found to be radiosensitive. Importantly, the suppression mediated by activated OKT4+ cells required the presence of radiosensitive cells contained within the resting OKT4+ population. Taken together, these results suggest that the OKT4+ subset of human T cells contains cells that can be activated to differentiate into suppressor cells independent of OKT8+ cells.

Antibodies↗
PubMed1981

Dissection of distinct human immunoregulatory T-cell subsets by a monoclonal antibody recognizing a cell surface antigen with wide tissue distribution.

A monoclonal antibody, PVR-11, was obtained after hybridization of X63Ag8.653 murine myeloma cells with spleen cells from a mouse immunized with human lymphocytes. It recognizes a 175,000- to 185,000-dalton surface antigen present on approximately 80% of normal human peripheral T lymphocytes, 50% of non-T non-B cells, and less than 10% of B cells as determined by complement-dependent microcytotoxicity. It is also present on various leukemia T cells, on some but not all T lymphoblastoid cell lines, and on a small fraction of some B lymphoblastoid cell lines. Some B-cell chronic lymphocytic leukemia cells also express the PVR-11 antigen. Functional analysis of normal human T lymphocytes demonstrated that the PVR-11-depleted T-cell subset contains the precursors of both cytotoxic and suppressor cells but lacks helper cells. On the other hand, cytotoxic effector T cells express the PVR-11 antigen. These results demonstrate that antigenic determinants with relatively wide tissue distribution can dissect functionally distinct human immunoregulatory T-cell subsets.

Antibodies↗
PubMed1981

Functional analysis of human T cell subsets defined by monoclonal antibodies. III. Regulation of helper factor production by T cell subsets.

In the present report we extended our previous studies demonstrating that obligatory T-T interactions are important in regulating human immune responses in vitro. Functionally distinct human T cell subsets were isolated by complement-mediated lysis using the monoclonal antibodies OKT4 and OKT8. Evidence was obtained that during allogeneic interactions, OKT4+, but not OKT8+, responder T cells are required to generate helper factor(s) capable of polyclonally activating human B cells independent of additional T cell help. Importantly, the alloantigen-induced helper factor(s) production and/or release was found to be suppressed by addition of graded numbers of radiosensitive OKT8+ cells. On the other hand, no evidence was obtained that supernatant derived from alloactivated OKT8+ cells could counterbalance the helper activity generated in the presence of supernatant from alloactivated OKT4+ cells. Furthermore, OKT8+ cells, known to suppress PWM-driven B cell differentiation in the presence of OKT4+ cells, do not suppress B cell differentiation induced by preformed helper factor even in the presence of OKT4+ cells. These data further underscore the importance of functional T-T interactions in immunoregulation in vitro and support the idea that the target of suppression of B cell differentiation, induced either by alloantigen-triggered helper factor or PWM, are OKT4+ cells and not B cells themselves.

Antibodies↗
PubMed1980

Suppressor cells in Hodgkin's disease and lung carcinoma.

Lymphocyte response to PHA was depressed in 9 of 14 cases of Hodgkin's disease (HD) and in 4 of 14 cases of lung carcinoma (LC). This depression was caused in one-third of the HD cases and in one-half of the LC cases by an excess of prostaglandin synthesis.

Adolescent↗
PubMed1980

[Immune monitoring of the cancer patient: suppressor cells and NK cells].

Immune monitoring in cancer patients consists mainly in the analysis of the immune deficiency, the search for immune modulators and the examination of antitumor reactions. Suppressor cells have been demonstrated in Hodgkin's disease and lung carcinoma. Azimexon, a synthetic immune adjuvant has shown in anergic cancer patients powerfull restorative properties. Spontaneous cell mediated cytoxicity can been enhanced by interferon of lymphokines injections.

Adjuvants, Immunologic↗
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↗
PubMedDate not supplied

Role of adherent suppressor cells in the depression of cell-mediated immunity in Hodgkin's disease and lung carcinoma.

The mechanism of the depression of cell-mediated immunity (CMI) in patients with Hodgkin's disease (HD) and lung carcinoma (LC) was investigated before any treatment. In 9 patients out of 14 with HD and in 4 patients out of 14 with LD, a depressed lymphocyte reactivity to phytohaemagglutinin (PHA) was observed. In 3 out of 9 patients with HD and in 2 out of 4 patients with LC who exhibited a depressed lymphocyte response to PHA, suppression caused by adherent cells and mediated by prostaglandins was evidenced. No relationship was found between this mechanism of suppression and depression of CMI in vivo as judged by skin tests to common recall antigens.

Adolescent↗
PubMedDate not supplied

Modulation of gut wall paf-acether and precursors by intestinal microflora.

Comparison between holoxenic and axenic mice led to the conclusion that the presence of an intestinal microflora produced a decrease in wall paf in conventional mouse caecum, whereas an increase in wall lyso-paf and alkyl-acyl-glycerophosphocholine (A-A-GPC) content was noticed. By contrast, the presence of flora had no significant incidence on wall paf, lyso-paf and A-A-GPC content of conventional mouse jejunum. Thus, the modulation of gut wall phospholipid composition by intestinal microflora is evidenced for the first time.

Animals↗