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Biomedical subjects

H S Warren

Publications and source records attributed to H S Warren.

At least 91 records · Page 5Linked to original sources
PubMed1985

Some interleukin-3 dependent mast-cell lines also respond to interleukin-2.

The haemopoietic stem cell line 32D cl-23 is alcian blue positive, Lyt 1+, and requires a growth factor, interleukin-3 (IL-3). This cell has now been shown to respond to interleukin-2 (IL-2). Antibodies directed against the murine interleukin-2 receptor blocked 3H-thymidine incorporation by 32D cl-23 cells grown in interleukin-2, but had no effect on 32D cl-23 in interleukin-3. Thus the receptor for interleukin-2 on 32D cl-23 cells may be similar to the interleukin-2 receptor on murine T cells. Similar results were obtained using a different basophil cell line 32D cl-5, but not using another basophil cell line, Rotundi, or factor dependent musocal type mast cells (P cells) derived from spleen.

Animals↗
PubMed1984

Differentiation of NK-like cells from OKT3-, OKT11+, and OKM1+ small resting lymphocytes by culture with autologous T cell blasts and lymphokine.

NK-like cells have been generated in vitro from a resting lymphocyte population of PBMC by 8 days culture with mitomycin C-treated autologous T cell blasts and lymphokine. The responder lymphocyte population was purified to the extent that it lacked classical NK cells, and lacked the precursors of MLC-derived NK-like cells and of lymphokine-activated killer cells. The NK-like cells were not generated when the responder lymphocytes were cultured with either T cell blasts or lymphokine alone. Thus, at least two signals are required for their activation. Metabolically inactive T cell blasts plus lymphokine were effective in stimulating the generation of NK-like cells, suggesting that a membrane determinant on the T cell blasts was involved in activation. The phenotype of the NK-like cells and their precursors was analyzed by monoclonal antibody and complement treatment. The phenotype of both precursor and effector cells was OKT3-, OKT11+, and OKM1+, with a distinct pattern of reactivity with OKT8 and Leu-7 for each individual donor tested. The NK-like cells were morphologically large granular lymphocytes, and they killed a variety of target cells. These studies show that signals provided by autologous T cell blasts and lymphokine are essential in triggering the differentiation of NK-like cells from appropriately purified resting lymphocytes. This mechanism of activation could occur in vivo, leading to the generation of NK cells subsequent to an antigen-specific T cell response.

Animals↗
PubMed1984

Different colony-stimulating factors are detected by the "interleukin-3"-dependent cell lines FDC-Pl and 32D cl-23.

The cell lines FDC-Pl and 32D cl-23 have previously been used as unique indicators for the growth-promoting activity of interleukin-3. We show that FDC-Pl cells respond to granulocyte/macrophage colony-stimulating factor (GM-CSF, CSF-2) as well as to interleukin-3. In keeping with this finding, FDC-Pl cells express the macrophage-specific marker, F4/80. FDC-Pl cells do not, however, respond to macrophage CSF (M-CSF, CSF-1). In contrast, 32D cl-23 cells do not respond to GM-CSF and lack F4/80. Instead, 32D cl-23 cells respond to an as yet undefined factor in conditioned medium (CM) from the primate T cell line, MLA-144, and CM from mitogen-stimulated human lymphocytes (HLCM). 32D cl-23 cells are Lyt-1+. Both FDC-Pl and 32D cl-23 cells consume interleukin-3, but only FDC Pl cells consume GM-CSF. Similarly, 32D cl-23, but not FDC-Pl, cells consume 32D cl-23 growth factor from MLA-144 CM and HLCM. Interleukin-3-dependent cell lines must therefore concurrently express different functional cell surface receptors for a variety of biochemically distinct growth factors.

Antibodies, Monoclonal↗
PubMed1983

Human bone marrow allograft recipients: production of, and responsiveness to, interleukin 2.

The production and utilization of interleukin 2 (IL 2) by peripheral blood mononuclear cells (PBMC) from 14 bone marrow allograft recipients was examined. PBMC from all patients were impaired in their ability to produce IL 2 when stimulated by phytohemagglutinin (PHA). On the average, the IL 2 activity produced by patients' PBMC was 8% of that from normal donors' PBMC. To examine the basis for this impaired T cell function in marrow recipients, the ability of a resting T lymphocyte population isolated from PBMC to respond to PHA and exogenously supplied IL 2 was analyzed. The proliferative response of resting T cells to PHA and IL 2, although low at early times post-transplant, reached near normal levels by 8 mo. Only two of 11 patients had normal numbers of precursor T cells that could respond. For all other patients the average number of precursor T cells was 10-fold lower than the average determined for normal donors. The impaired production of IL 2 by patients' PBMC may be due to this low precursor frequency. For some patients the rate and/or extent of clonal expansion of activated T cells appears to be greater than that of normal donors. The data suggest that the therapeutic application of IL 2 to such patients is unlikely to be successful in overcoming defects of T cell function before 8 mo post-marrow transplant.

Adult↗
PubMed1982

Human allogeneic responses: lymphokine requirement for the in vitro generation of specific cytotoxic responses to a malignant melanoma cell line.

Requirements for the in vitro generation of specific cytotoxic responses by human T-lymphocytes to an allogeneic malignant melanoma cell line (MM-170) have been examined. The responder T-lymphocytes used were isolated from peripheral blood and were essentially free of non-specific cytotoxic effector cells and their precursors. MM-170 alone was found to be an inadequate stimulator of cytotoxic responses. Stimulation did occur in cultures with both MM-170 and an Interleukin-2 containing human lymphokine supernatant. The cytotoxic effector cells generated were specific for MM-170 when the MM-170 cells used for stimulation had been metabolically inactivated by glutaraldehyde treatment.

Antigens, Neoplasm↗
PubMed1981

A method for the production and quantitative assay of human lymphokine preparations.

A procedure for the preparation and assay of a human lymphokine supernatant is described. Tonsillar lymphocytes at a concentration of 2 X 10(7)/ml in a serum-free medium are incubated for 2 h with PHA-P, washed free of unbound mitogen and incubated for a further 17 h. The supernatant is harvested and concentrated, and the active protein fraction is absorbed to and eluted from a column of hydroxylapatite. The eluate is desalted and sterile filtered. The preparations contain active material released from 10(8) cells in 1 ml and do not contain residual PHA-P. The most active preparations are obtained using PHA-P as the mitogen and at concentrations of 25-50 microgram/ml during the 2 h pulsing period. Activity is assessed by a quantitative assay based on the maintenance of mitogen activated blast cells in culture for 2 days.

Cells, Cultured↗
PubMed1981

The generation of specific cytotoxic responses by human lymphocytes requires antigen and activities provided by a lymphokine supernatant.

The requirements for the generation of specific cytotoxic responses by human lymphocytes have been investigated using as a model system the response to the ultraviolet light-killed mouse tumour P815. These requirements are antigen (P815UV) and activities provided by a human lymphokine (LK) supernatant. Cells that give rise to non-specific cytotoxicity can be separated on discontinuous Percoll density gradients after a 3-day incubation of peripheral blood leucocytes with the lymphokine supernatant. Cells from which specific cytotoxic responses can subsequently be generated in the presence of P815UV and LK sediment at a higher density.

Animals↗
PubMed1981

Lymphokine production by peripheral blood leucocytes: quantitation of T-cell growth factor activity for assessment of immune response capability.

Mitogen stimulation of as few as 200,000 human peripheral blood leucocytes (PBL) in 0.2 ml volumes produces highly active lymphokine supernatants. The lymphokine activity measured is T-cell growth factor. Under optimum conditions of PHA-P concentration, serum source and concentration, and time, activity is detectable to a dilution of between 1/250 and 1/700 for lymphokine supernatants from PBL of normal donors. Lymphokine supernatants prepared from PBL of donors previously treated with the immunosuppressive regimes of radiotherapy and/or chemotherapy had activities that were between 13% and 66% of normal controls. Lymphokine production as a quantitative measure of immune capability is discussed.

Adolescent↗
PubMed1980

An improved assay for interleukin 2 (lymphocyte growth factor) produced by mitogen-activated lymphocytes.

The continued proliferation of activated T cells requires the presence of a lymphocyte growth factor in the culture medium. This study describes a rapid, highly reproducible assay to quantitatively measure levels of this lymphokine. The use of Concanavalin-A blast cells given this assay a high degree of flexibility and convenience. It is shown that the lymphokine measured is interleukin 2. The presence of an inhibitor in the supernatant of mitogen activated lymphocytes and the species specificity of the factor are demonstrated.

Animals↗
PubMed1979

A high frequency of cytotoxic precursor cells for a syngeneic tumour.

The average frequency of cytotoxic precursor cells in DBA/2 lymph node cell preparations reactive to the syngeneic tumour P815 has been determined as 1 in 2000. This frequency is similar to the precursor frequency for an allogeneic tumour EL-4. The normal lack of response of DBA/2 lymph node cells to the syngeneic tumour P815 in vitro cannot be attributed to a lack of cytotoxic precursor cells. We conclude that in this tumour-host system non-immunogenicity reflects a defect at the inductive step.

Animals↗
PubMed1978

Cytotoxic T cell responses to a syngeneic tumour: conditions for primary activation in vitro.

Primary cytotoxic responses of DBA/2 lymph node cells to a syngeneic tumour (the mastocytoma P815) have been generated in vitro. The development of these responses is dependent on the addition of a soluble factor (CSCS) which is produced by concanavalin A-activated spleen cells. The response is mediated by T lymphocytes, can be detected at low effector to target cell ratios and is directed against P815 tumour-associated antigens.

Animals↗
PubMed1978

Immunological induction of T lymphocytes: role of antigen and the lymphocyte costimulator.

In vitro T cell activation requires both antigen presentation and a second stimulus provided by the lymphocyte costimulator. Neither alone is sufficient to induce specific T cell activation. The S+ phenotype of stimulating cells is dependent on the metabolic activity of these cells. This finding is consistent with the notion that production and/or release of the costimulator is a function of metabolically active cells. The costimulator acts at an early stage of the interaction between lymphocyte and antigen, and the costimulator, or a separate maintenance factor, is required throughout the culture period for the expression of full cytotoxic activity. The lymphocyte costimulator is not strain specific but is phylogenetically specific. The activation of cytotoxic T cells by S+ cells is also phylogenetically specific, and this specificity of cellular activation can be accounted for by the species specificity of the lymphocyte costimulator.

Animals↗