Regulation of 4-1BB expression by cell-cell interactions and the cytokines, interleukin-2 and interleukin-4

Karen Pollok, Seung H. Kim, Byoung S. Kwon

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

4-1BB expression increased gradually following T cell activation, and by day 3 post-stimulation with immobilized anti-CD3 (anti-CD3i) or concanavalin A (Con A), splenic T cells were routinely 35-45% 4-1BB+ by now cytometric analysis. 4-1BB was expressed on activated CD8+, CD4+, CD28+ and CD45RB+ T cells. Optimal 4-1BB expression was seen by day 6 post-stimulation and was cell density dependent. When T cells were cultured for 6 days at 1 x 106/well in a 24-well plate with anti-CD3i, 82% of the cells were 4-1BB+. In contrast, at lower cell densities (4 x 105, 2 x 105 and 1 x 105), optimal 4-1BB expression was observed only if the cultures were supplemented with recombinant interleukin-2 (IL-2) or recombinant IL-4 (IL-4). In agreement, with these results, modes of inducing endogenous IL-2 production such as cross-linking the costimulatory molecule, CD28, or the addition of syngeneic accessory cells to T cells activated with anti-CD3i, resulted in high levels of 4-1BB expression, The addition of interleukin-1α (IL-1α) or interferon-γ (IFN-γ) did not increase 4-1BB expression on anti-CD3i-activated T cells. In addition, if T cells were incubated with IL-2, IL-4, IL-1α, IFN-γ or anti-CD28 alone, no 4-1BB expression was induced. T cells activated with soluble anti-CD3 (anti-CD3s) in the presence of IL-2, IL-4, or accessory cells, did not express higher levels of 4-1BB on their cell surface. These data suggest that initial events crucial for efficient T cell activation, such as signals delivered through the T cell receptor/CD3 complex and tie CD28 molecule, are instrumental in regulating subsequent 4-1BB expression.

Original languageEnglish (US)
Pages (from-to)488-494
Number of pages7
JournalEuropean Journal of Immunology
Volume25
Issue number2
DOIs
StatePublished - Feb 1995
Externally publishedYes

Fingerprint

Cell Communication
Interleukin-4
Interleukin-2
Cytokines
T-Lymphocytes
Interleukin-1
Interferons
Cell Count
CD3 Antigens
Concanavalin A
T-Cell Antigen Receptor

Keywords

  • 4-1BB
  • Interleukin-2
  • Interleukin-4
  • T lymphocyte

ASJC Scopus subject areas

  • Immunology

Cite this

Regulation of 4-1BB expression by cell-cell interactions and the cytokines, interleukin-2 and interleukin-4. / Pollok, Karen; Kim, Seung H.; Kwon, Byoung S.

In: European Journal of Immunology, Vol. 25, No. 2, 02.1995, p. 488-494.

Research output: Contribution to journalArticle

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abstract = "4-1BB expression increased gradually following T cell activation, and by day 3 post-stimulation with immobilized anti-CD3 (anti-CD3i) or concanavalin A (Con A), splenic T cells were routinely 35-45{\%} 4-1BB+ by now cytometric analysis. 4-1BB was expressed on activated CD8+, CD4+, CD28+ and CD45RB+ T cells. Optimal 4-1BB expression was seen by day 6 post-stimulation and was cell density dependent. When T cells were cultured for 6 days at 1 x 106/well in a 24-well plate with anti-CD3i, 82{\%} of the cells were 4-1BB+. In contrast, at lower cell densities (4 x 105, 2 x 105 and 1 x 105), optimal 4-1BB expression was observed only if the cultures were supplemented with recombinant interleukin-2 (IL-2) or recombinant IL-4 (IL-4). In agreement, with these results, modes of inducing endogenous IL-2 production such as cross-linking the costimulatory molecule, CD28, or the addition of syngeneic accessory cells to T cells activated with anti-CD3i, resulted in high levels of 4-1BB expression, The addition of interleukin-1α (IL-1α) or interferon-γ (IFN-γ) did not increase 4-1BB expression on anti-CD3i-activated T cells. In addition, if T cells were incubated with IL-2, IL-4, IL-1α, IFN-γ or anti-CD28 alone, no 4-1BB expression was induced. T cells activated with soluble anti-CD3 (anti-CD3s) in the presence of IL-2, IL-4, or accessory cells, did not express higher levels of 4-1BB on their cell surface. These data suggest that initial events crucial for efficient T cell activation, such as signals delivered through the T cell receptor/CD3 complex and tie CD28 molecule, are instrumental in regulating subsequent 4-1BB expression.",
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N2 - 4-1BB expression increased gradually following T cell activation, and by day 3 post-stimulation with immobilized anti-CD3 (anti-CD3i) or concanavalin A (Con A), splenic T cells were routinely 35-45% 4-1BB+ by now cytometric analysis. 4-1BB was expressed on activated CD8+, CD4+, CD28+ and CD45RB+ T cells. Optimal 4-1BB expression was seen by day 6 post-stimulation and was cell density dependent. When T cells were cultured for 6 days at 1 x 106/well in a 24-well plate with anti-CD3i, 82% of the cells were 4-1BB+. In contrast, at lower cell densities (4 x 105, 2 x 105 and 1 x 105), optimal 4-1BB expression was observed only if the cultures were supplemented with recombinant interleukin-2 (IL-2) or recombinant IL-4 (IL-4). In agreement, with these results, modes of inducing endogenous IL-2 production such as cross-linking the costimulatory molecule, CD28, or the addition of syngeneic accessory cells to T cells activated with anti-CD3i, resulted in high levels of 4-1BB expression, The addition of interleukin-1α (IL-1α) or interferon-γ (IFN-γ) did not increase 4-1BB expression on anti-CD3i-activated T cells. In addition, if T cells were incubated with IL-2, IL-4, IL-1α, IFN-γ or anti-CD28 alone, no 4-1BB expression was induced. T cells activated with soluble anti-CD3 (anti-CD3s) in the presence of IL-2, IL-4, or accessory cells, did not express higher levels of 4-1BB on their cell surface. These data suggest that initial events crucial for efficient T cell activation, such as signals delivered through the T cell receptor/CD3 complex and tie CD28 molecule, are instrumental in regulating subsequent 4-1BB expression.

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