Regulation of Ig class secretion by soluble products of certain T-cell lines.
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Animals↗
Biomedical subjects
P Sideras
Publications and source records attributed to P Sideras.
Development and continuous growth in culture of interleukin 2-producer lymphocytes from athymic nu/nu mice.
Splenocytes of nu/nu mice treated with serum thymic factor (FTS) for 3 or more days followed by stimulation with either phorbol myristate acetate (PMA) or concanavalin A (Con A) produced interleukin 2 (IL 2) as determined in two indicator systems, namely, support of growth of IL 2-dependent T cells and promotion of Con A-initiated mitogenesis of thymocytes. However, neither mitogens nor FTS alone could induce nude mice cells to product IL 2. Supernatants derived from the tumor cell line WEHI-3 (WEHI-3 conditioned media) induced and supported continuous growth in culture of Thy-1.2+, Lyt-1+2- lymphocytes from athymic nude mice capable of producing IL 2 after their stimulation by either PMA or Con A. The growth of these IL 2-producer cell lines strickly depends on the presence of WEHI-3 conditioned media, as in the absence of it they die 24-48 h later. In addition, WEHI-3 conditioned media have been supporting the growth of IL 2-producer cell lines derived from nude mice for 3 1/2 months. The helper factor contained in WEHI-3 conditioned media responsible for the above biological activity has an apparent mol. wt. of approximately 40 000 as determined by Sephadex G-100 chromatography and lacks IL 1 and IL 2 activities, but efficiently supports the growth of IL 2-producer cells derived from nude mice and the peripheral blood of normal human volunteers. These results indicate that the helper factor in WEHI-3 conditioned media which enables the generation and continuous proliferation in culture of IL 2-producer cells in nude mice is distinct from interleukin 1, IL 2 and FTS (mol. wt. 864). Finally, the possibly functional relationship of FTS and the helper factor produced by WEHI-3 cells is discussed.
Animals↗
Accessory function of human tumor cell lines. I. Production of interleukin 1 by the human histiocytic lymphoma cell line U-937.
The established human histiocytic lymphoma cell line U-937 spontaneously produced a factor with biological activity similar to that ascribed to interleukin 1 (IL 1). Actually, supernatants from U-937 cells promoted proliferation of thymocytes initiated by concanavalin A (Con A) and replaced the requirement of accessory cells for activation of highly purified circulating T lymphocytes induced by Con A. Phorbol myristate acetate (PMA) significantly increased the titers of the helper factor produced by U-937 cells as compared to that secreted by non-PMA-treated U-937 cells or PMA-stimulated P388D1 murine macrophage tumor cells. Generally U-937 cells did not secrete detectable IL 1 activity during the first 24-48 h of culture. However, after this initial period the level of IL 1 activity increased and reached a maximum at 5-6 days of culture. Finally, the helper factor released by U-937 cells had an apparent mol. wt. of 12000-15000 as determined by Sephadex G-100 chromatography and lacked interleukin 2 activity as shown by its inability to support growth of IL 2-addicted T cell lines. To our knowledge this is the first report of an established human cell line capable of producing IL 1.
Animals↗
Cloning of cDNA encoding the murine IgG1 induction factor by a novel strategy using SP6 promoter.
Complementary DNA encoding the IgG1 induction factor, the first lymphokine directed to B lymphocytes, from a murine T-cell line has been cloned using a new strategy. The putative primary amino-acid sequence was deduced from the nucleotide sequence determined. The lymphokine synthesized by the direction of this cloned cDNA has many other functions, such as production of B-cell growth factor-1 and induction of Ia on B cells.
Amino Acid Sequence↗
Cloning of complementary DNA encoding T-cell replacing factor and identity with B-cell growth factor II.
Proliferation and maturation of antigen-stimulated B cells are regulated by several soluble factors derived from macrophages and T cells. These soluble factors are functionally divided into two groups: B-cell growth factor (BCGF), thought to be involved in B-cell proliferation; and B-cell differentiation factor (BCDF), responsible for maturation of activated B cells into immunoglobulin-secreting cells. This classification needs to be re-examined in the light of the recent cloning of complementary DNA encoding IgG1 induction factor (interleukin-4, IL-4) from the 2.19 mouse T-cell line. Recombinant IL-4 has BCGF and BCDF activities and affects B cells, T cells and mast cells (refs 7, 8; our unpublished data). Another well-characterized B-cell factor is T-cell replacing factor (TRF), which, when secreted by the murine T-cell hybridoma B151K12, is defined by two activities: induction of IgM secretion by BCL1 leukaemic B-cell line; and induction of secondary anti-dinitrophenol (DNP) immunoglobulin G (IgG) synthesis in vitro by DNP-prime B cells. Although TRF from B151K12 was classified as BCDF, purified TRF has BCGF-II activity. To elucidate the molecular properties of TRF we isolated cDNA encoding TRF from the 2.19 T-cell line and report here the structure and multiple activities of this lymphokine.
Animals↗
Development of CLL in individuals with mild lymphocytosis, without bone marrow infiltration, but with evidence of a monoclonally expanded population in peripheral blood.
Mild lymphocytosis (< 10 x 10(9)/L) is a common finding in routine blood tests. When it persists, it raises the question of whether this disorder is an early manifestation of chronic lymphocytic leukemia (CLL). If it is accompanied by bone marrow infiltration, it can be safely considered as a sign of CLL. The aim of this study was to analyze retrospectively the usefulness of immunophenotyping and immunogenotyping for early detection of lymphocyte clonality in ambiguous cases of lymphocytosis without bone marrow infiltration. Twenty-six healthy individuals, 47 to 77 years old, with an absolute lymphocyte count (ALC) at the "onset" of the disorder between 4 x 10(9)/L and 9 x 10(9)/L, without marrow infiltration, were studied and followed for a period of 31 to 51 months. CD19, CD20, CD5, CD2, CD4, CD8 surface markers and amplification of the Ig heavy chain CDR-3 locus were used for immunophenotypic and genotypic analysis, respectively. Our studies indicate that immunophenotyping alone is sufficient and superior to CDR-3 locus amplification for the early detection of lymphocyte clonality in peripheral blood. Furthermore, the high frequency of CLL development in individuals with established monoclonality strongly suggests that patients with mild borderline lymphocytosis, even without bone marrow infiltration, have to be followed for progression to CLL and its possible complications.
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