The role of mitogenic lectins in T-cell triggering

Larsson, Eva‐Lotta; Coutinho, António

doi:10.1038/280239a0

Cited by 192 publications

(79 citation statements)

References 10 publications

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“…T cells were stimulated with Con A for 8-12 h in serum-containing media, washed, and recultured in serum-free media. This duration of stimulation is sufficient for cellular activation and IL-2-R expression, but not for subsequent progression into S phase unless exogenous IL-2 is present (17,18). Fig.…”

Section: Tgf-t3 Suppresses Il-2-dependent T Cell Proliferation and Pamentioning

confidence: 99%

Production of transforming growth factor beta by human T lymphocytes and its potential role in the regulation of T cell growth.

Kehrl¹,

Wakefield²,

Roberts³

et al. 1986

The Journal of Experimental Medicine

1,479

615

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This study examines the potential role of transforming growth factor beta (TGF-beta) in the regulation of human T lymphocyte proliferation, and proposes that TGF-beta is an important autoregulatory lymphokine that limits T lymphocyte clonal expansion, and that TGF-beta production by T lymphocytes is important in T cell interactions with other cell types. TGF-beta was shown to inhibit IL-2-dependent T cell proliferation. The addition of picograms amounts of TGF-beta to cultures of IL-2-stimulated human T lymphocytes suppressed DNA synthesis by 60-80%. A potential mechanism of this inhibition was found. TGF-beta inhibited IL-2-induced upregulation of the IL-2 and transferrin receptors. Specific high-affinity receptors for TGF-beta were found both on resting and activated T cells. Cellular activation was shown to result in a five- to sixfold increase in the number of TGF-beta receptors on a per cell basis, without a change in the affinity of the receptor. Finally, the observations that activated T cells produce TGF-beta mRNA and that TGF-beta biologic activity is present in supernatants conditioned by activated T cells is strong evidence that T cells themselves are a source of TGF-beta. Resting T cells were found to have low to undetectable levels of TGF-beta mRNA, while PHA activation resulted in a rapid increase in TGF-beta mRNA levels (within 2 h). Both T4 and T8 lymphocytes were found to make mRNA for TGF-beta upon activation. Using both a soft agar assay and a competitive binding assay, TGF-beta biologic activity was found in supernatants conditioned by T cells; T cell activation resulted in a 10-50-fold increase in TGF-beta production. Thus, TGF-beta may be an important antigen-nonspecific regulator of human T cell proliferation, and important in T cell interaction with other cell types whose cellular functions are modulated by TGF-beta.

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Section: Tgf-t3 Suppresses Il-2-dependent T Cell Proliferation and Pamentioning

confidence: 99%

Production of transforming growth factor beta by human T lymphocytes and its potential role in the regulation of T cell growth.

Kehrl¹,

Wakefield²,

Roberts³

et al. 1986

The Journal of Experimental Medicine

1,479

615

View full text Add to dashboard Cite

show abstract

“…Moreover, the process of T cell activation has been well studied in vitro (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13). Alloantigenic activation of T cells in vitro leads to the induction of IL-2 receptors on T cell surface membranes, and the interaction of IL-2 with these receptors is required for T cell proliferation.…”

Section: Discussionmentioning

confidence: 99%

Administration of an anti-interleukin 2 receptor monoclonal antibody prolongs cardiac allograft survival in mice.

Kirkman¹,

Barrett²,

Gaulton³

et al. 1985

The Journal of Experimental Medicine

179

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The immune response to a vascularized allograft involves a complex series of events, including T cell activation. A critical marker of T cell activation is the acquisition of stereospecific membrane receptors for the lymphokine, interleukin 2 (IL-2) (1-4). While resting T cells lack IL-2 receptors, in vitro studies (5,6) indicate that essentially all lectin-or alloantigen-stimulated proliferating T cells express the IL-2 receptor. Moreover, the interaction of IL-2 with receptorbearing cells is required for the clonal expansion of activated T cells (1-13). Whereas engagement of the T cell receptor for antigen is the first step in T cell activation, the interaction of IL-2 with the newly expressed IL-2 receptor is a requisite step in the common pathway of activation of all T cells. The extension of these in vitro findings to the process of allograft rejection in vivo has not been extensively studied. IL-2 is necessary to reconstitute the acute rejection response in vivo in T cell-deprived rats (14). However, direct evidence in vivo that the IL-2 receptor is involved in allograft rejection has been lacking.The rat monoclonal antibody (mAb) M7/20 binds to the murine IL-2 receptor, as demonstrated by its capacity to bind activated but not resting T cells in flow cytometry experiments, to prevent IL-2-mediated DNA synthesis in an IL-2-dependent cytotoxic T lymphocyte cell line, to precipitate an N-glycosylated 58 kilodalton glycoprotein, and to competitively inhibit binding of radiolabelled IL-2 (15). As such, it offers an opportunity to direct immunosuppressive therapy selectively against IL-2 receptor-bearing cells during allograft rejection. In this report, we examine the effect of administration of M7/20 on survival of cardiac allografts in mice. Materials and MethodsAnimals. Inbred male mice, weighing 20-25 gm, of strains C57BL/10, B10.BR, and B10.AKM (The Jackson Laboratory, Bar Harbor, ME) were used throughout. These strains are completely mismatched for the H-2 locus, but share the same genetic background.Operative Technique. Vascularized, heterotopic heart allografts were performed as

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“…Induction of peak IL-2 levels in unseparated lymphoid cell populations occurs 12-24 h after stimulation with appropriate mitogens. 13,14) Thus IL-2 levels were determined not only after culture for 72 h but also after culture for 20 h, however, the cytokine was not detected (data not shown).…”

Section: Effects Of Lumin On Ifn-g G Production By Lps-stimulated Murinementioning

confidence: 99%

Lumin, a Cyanine Dye, Enhances Interleukin 12-Dependent Interferon Gamma Production by Lipopolysaccharide-Stimulated Mouse Splenocytes.

Kunikata

Ishihara

Ushio

et al. 2002

Biological & Pharmaceutical Bulletin

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Lumin was orally administered to mice daily for 3 d, and on the day following the final administration, mice were sacrificed and splenocytes were stimulated with lipopolysaccharide (LPS). Splenocytes obtained from lumin-treated mice showed enhanced production of interferon g g (IFN-g g) and increased percentages of CD3 ؉ cells. Although T cells are considered to be the source of IFN-g g, it is unlikely that LPS directly stimulates T cells. Next we performed neutralization experiments using a monoclonal antibody (mAb) against interleukin (IL-)12 because this cytokine, which is produced by macrophages, has the direct ability to induce IFN-g g production and the proliferation of activated T cells. This antibody inhibited IFN-g g production by splenocytes. We thus show that orally administered lumin enhances IFN-g g production by splenocytes when the latter are stimulated with LPS, a phenomenon that was observed in correlation with activation of T cells by IL-12, that is produced by macrophages.

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The role of mitogenic lectins in T-cell triggering

Cited by 192 publications

References 10 publications

Production of transforming growth factor beta by human T lymphocytes and its potential role in the regulation of T cell growth.

Production of transforming growth factor beta by human T lymphocytes and its potential role in the regulation of T cell growth.

Administration of an anti-interleukin 2 receptor monoclonal antibody prolongs cardiac allograft survival in mice.

Lumin, a Cyanine Dye, Enhances Interleukin 12-Dependent Interferon Gamma Production by Lipopolysaccharide-Stimulated Mouse Splenocytes.

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