Transferrin can replace serum for <i>in vitro</i> growth of mitogen‐stimulated T lymphocytes

Dillner‐Centerlind, M.‐L.; Hammarström, Sten; Perlmann, Peter

doi:10.1002/eji.1830091207

Cited by 81 publications

(38 citation statements)

References 25 publications

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“…In contrast, free Tf did not interfere with the activation of DO-BW using the uncoupled OVA. In fact, Tf stimulated IL-2 production in the presence of the OVA peptide, supporting the idea that Tf is required for T cell activation (39). Because the serum concentration of saturated Tf is ϳ6.5 M (40), much lower than the concentrations we are testing in this study, this result suggests that the Tf-peptide conjugates would be effectively taken-up and presented in vivo even in the presence of the normal levels of endogenous Tf.…”

Section: Uptake Of the Tf-peptide Conjugates Occurs Through The Trsupporting

confidence: 78%

Enhancement of MHC Class II-Restricted Responses by Receptor-Mediated Uptake of Peptide Antigens

Zaliauskiene

Kang

Sparks

et al. 2002

The Journal of Immunology

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Peptides, either as altered peptide ligands, competitors, or vaccines, offer an outstanding potential for regulating immune responses because of their exquisite specificity. However, a major problem associated with peptide therapies is that they are poorly taken up by APCs. Because of poor bioavailability, high concentrations and repeated treatments are required for peptide therapies in vivo. To circumvent this problem, we tested whether covalently coupling a peptide T cell determinant, OVA323–339, to transferrin (Tf) enhances APC uptake and presentation as monitored by Th cell activation. Functional analysis of the Tf-peptide conjugates revealed that the conjugates were presented 10,000- and 100-fold more effectively by B cells than intact Ag and free peptide, respectively. Furthermore, we demonstrate that the Tf-peptide conjugates are taken up by B cells through a receptor-mediated process and subsequently delivered to the lysosomal compartment. Using an adoptive transfer assay, we show that that the Tf-peptide complexes are 100-fold more effective in vivo than the free peptide in activating CD4+ T cells by following an early activation marker, CD69. Our results demonstrate that coupling peptides to Tf enhances peptide presentation, thereby making it possible to take full advantage of peptide-specific therapies in modulating T cell responses.

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Section: Uptake Of the Tf-peptide Conjugates Occurs Through The Trsupporting

confidence: 78%

Enhancement of MHC Class II-Restricted Responses by Receptor-Mediated Uptake of Peptide Antigens

Zaliauskiene

Kang

Sparks

et al. 2002

The Journal of Immunology

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“…One of the consequences of this interaction is an upregulation in cellsurface membrane IL-2-R (20, 21). IL-2 has also been shown (22)(23)(24) to be an important signal in the upregulation of another receptor, the transferrin receptor, which is thought to be important in cellular growth and is found on rapidly dividing cells. A potential mechanism whereby TGF-/3 might inhibit the growth of T cells is by interfering with the normal expression of either of these receptors.…”

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

1,473

609

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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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“…The liver is the major site of Tf synthesis (1,3). Tf is a growth factor required for proliferating normal and malignant cells (4)(5)(6)(7)(8); it is an essential component of defined medium used for growth of lymphocytes in vitro. Tf enters cells by receptor-mediated endocytosis (9).…”

Section: Introductionmentioning

confidence: 99%

Transferrin synthesis by inducer T lymphocytes.

Lum¹,

Infante²,

Makker³

et al. 1986

J. Clin. Invest.

102

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Transferrin can replace serum for in vitro growth of mitogen‐stimulated T lymphocytes

Cited by 81 publications

References 25 publications

Enhancement of MHC Class II-Restricted Responses by Receptor-Mediated Uptake of Peptide Antigens

Enhancement of MHC Class II-Restricted Responses by Receptor-Mediated Uptake of Peptide Antigens

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

Transferrin synthesis by inducer T lymphocytes.

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