Staphylococcus enterotoxin A modulates interleukin 15-induced signaling and mitogenesis in human T cells

J Gerwien; K Kaltoft; M Nielsen; M B Nielsen; A Svejgaard; C Geisler; C Röpke; N Odum

Staphylococcus enterotoxin A modulates interleukin 15-induced signaling and mitogenesis in human T cells

J Gerwien, K Kaltoft, M Nielsen, M B Nielsen, A Svejgaard, C Geisler, C Röpke, N Odum

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

3 Citationer (Scopus)

Abstract

Udgivelsesdato: 1998-Feb

Originalsprog	Engelsk
Tidsskrift	HLA
Vol/bind	51
Udgave nummer	2
Sider (fra-til)	164-73
Antal sider	9
ISSN	2059-2302
Status	Udgivet - 1998

Bibliografisk note

Keywords: 1-Phosphatidylinositol 3-Kinase; Cell Division; Cell Line; Cyclosporine; Enterotoxins; Enzyme Inhibitors; Humans; Interleukin-15; Interleukin-2; Lymphocyte Activation; Phosphorylation; Protein Kinase C; Receptors, Interleukin-15; Receptors, Interleukin-2; Signal Transduction; T-Lymphocytes

Citationsformater

@article{810fbbc0b0a411ddb538000ea68e967b,

title = "Staphylococcus enterotoxin A modulates interleukin 15-induced signaling and mitogenesis in human T cells",

abstract = "T cells expressing the appropriate T-cell receptor Vbeta chain proliferate in response to Staphylococcus enterotoxin A (SEA) pulsed antigen-presenting cells (APC), whereas other T cells do not (SEA {"}non-responders{"}). Activated human T cells express MHC class II molecules that are high affinity receptors for SEA. Here we show that, in the absence of APC, SEA induces a profound inhibition of IL-15-driven proliferation in MHC class II+, human SEA-{"}responder{"} T-cell lines. In contrast, proliferation induced by phorbol esther (PMA) was enhanced by SEA. The inhibitory effect on cytokine-mediated mitogenesis correlates with an inhibition of IL-2Rbeta expression and ligand-induced tyrosine phosphorylation of IL-2R. Cyclosporin A (CyA), an inhibitor of the protein phosphatase (PP2B) calcineurin, strongly inhibits the SEA-induced modulations of cytokine receptor expression. Moreover, CyA inhibits both the anti-mitogenic effect of SEA on cytokine-induced proliferation and the pro-mitogenic effect of PMA. In contrast, inhibitors of PP1, PP2A, protein kinase C (PKC), phosphatidyl-inositol-3-kinase (PI-3K) and mammalian target of rapamycin (mTOR) are unable to inhibit the effects of SEA. In a SEA {"}non-responder{"} T-cell clone obtained from the affected skin of a patient with psoriasis vulgaris, SEA does not inhibit IL-2Rbeta expression and IL-15-driven proliferation. On the contrary, SEA enhances IL-15- and IL-2-induced proliferation via a CyA-sensitive pathway in this T-cell clone. In conclusion, the present data show that (i) SEA selectively inhibits IL-15- (but not PMA-) mediated proliferation in SEA {"}responder{"} T cells, (ii) SEA enhances cytokine-driven growth in psoriasis T cells with a {"}non-responder{"} phenotype, and (iii) crosstalk between SEA receptors and the IL-15R (and IL-2R) pathway is mediated via a PP2B-dependent and PP1/PP2A-, PKC-, PI-3 kinase- and mTOR-independent pathway in human T-cell lines.",

author = "J Gerwien and K Kaltoft and M Nielsen and Nielsen, {M B} and A Svejgaard and C Geisler and C R{\"o}pke and N Odum",

note = "Keywords: 1-Phosphatidylinositol 3-Kinase; Cell Division; Cell Line; Cyclosporine; Enterotoxins; Enzyme Inhibitors; Humans; Interleukin-15; Interleukin-2; Lymphocyte Activation; Phosphorylation; Protein Kinase C; Receptors, Interleukin-15; Receptors, Interleukin-2; Signal Transduction; T-Lymphocytes",

year = "1998",

language = "English",

volume = "51",

pages = "164--73",

journal = "HLA",

issn = "2059-2302",

publisher = "Wiley",

number = "2",

}

TY - JOUR

T1 - Staphylococcus enterotoxin A modulates interleukin 15-induced signaling and mitogenesis in human T cells

AU - Gerwien, J

AU - Kaltoft, K

AU - Nielsen, M

AU - Nielsen, M B

AU - Svejgaard, A

AU - Geisler, C

AU - Röpke, C

AU - Odum, N

N1 - Keywords: 1-Phosphatidylinositol 3-Kinase; Cell Division; Cell Line; Cyclosporine; Enterotoxins; Enzyme Inhibitors; Humans; Interleukin-15; Interleukin-2; Lymphocyte Activation; Phosphorylation; Protein Kinase C; Receptors, Interleukin-15; Receptors, Interleukin-2; Signal Transduction; T-Lymphocytes

PY - 1998

Y1 - 1998

N2 - T cells expressing the appropriate T-cell receptor Vbeta chain proliferate in response to Staphylococcus enterotoxin A (SEA) pulsed antigen-presenting cells (APC), whereas other T cells do not (SEA "non-responders"). Activated human T cells express MHC class II molecules that are high affinity receptors for SEA. Here we show that, in the absence of APC, SEA induces a profound inhibition of IL-15-driven proliferation in MHC class II+, human SEA-"responder" T-cell lines. In contrast, proliferation induced by phorbol esther (PMA) was enhanced by SEA. The inhibitory effect on cytokine-mediated mitogenesis correlates with an inhibition of IL-2Rbeta expression and ligand-induced tyrosine phosphorylation of IL-2R. Cyclosporin A (CyA), an inhibitor of the protein phosphatase (PP2B) calcineurin, strongly inhibits the SEA-induced modulations of cytokine receptor expression. Moreover, CyA inhibits both the anti-mitogenic effect of SEA on cytokine-induced proliferation and the pro-mitogenic effect of PMA. In contrast, inhibitors of PP1, PP2A, protein kinase C (PKC), phosphatidyl-inositol-3-kinase (PI-3K) and mammalian target of rapamycin (mTOR) are unable to inhibit the effects of SEA. In a SEA "non-responder" T-cell clone obtained from the affected skin of a patient with psoriasis vulgaris, SEA does not inhibit IL-2Rbeta expression and IL-15-driven proliferation. On the contrary, SEA enhances IL-15- and IL-2-induced proliferation via a CyA-sensitive pathway in this T-cell clone. In conclusion, the present data show that (i) SEA selectively inhibits IL-15- (but not PMA-) mediated proliferation in SEA "responder" T cells, (ii) SEA enhances cytokine-driven growth in psoriasis T cells with a "non-responder" phenotype, and (iii) crosstalk between SEA receptors and the IL-15R (and IL-2R) pathway is mediated via a PP2B-dependent and PP1/PP2A-, PKC-, PI-3 kinase- and mTOR-independent pathway in human T-cell lines.

AB - T cells expressing the appropriate T-cell receptor Vbeta chain proliferate in response to Staphylococcus enterotoxin A (SEA) pulsed antigen-presenting cells (APC), whereas other T cells do not (SEA "non-responders"). Activated human T cells express MHC class II molecules that are high affinity receptors for SEA. Here we show that, in the absence of APC, SEA induces a profound inhibition of IL-15-driven proliferation in MHC class II+, human SEA-"responder" T-cell lines. In contrast, proliferation induced by phorbol esther (PMA) was enhanced by SEA. The inhibitory effect on cytokine-mediated mitogenesis correlates with an inhibition of IL-2Rbeta expression and ligand-induced tyrosine phosphorylation of IL-2R. Cyclosporin A (CyA), an inhibitor of the protein phosphatase (PP2B) calcineurin, strongly inhibits the SEA-induced modulations of cytokine receptor expression. Moreover, CyA inhibits both the anti-mitogenic effect of SEA on cytokine-induced proliferation and the pro-mitogenic effect of PMA. In contrast, inhibitors of PP1, PP2A, protein kinase C (PKC), phosphatidyl-inositol-3-kinase (PI-3K) and mammalian target of rapamycin (mTOR) are unable to inhibit the effects of SEA. In a SEA "non-responder" T-cell clone obtained from the affected skin of a patient with psoriasis vulgaris, SEA does not inhibit IL-2Rbeta expression and IL-15-driven proliferation. On the contrary, SEA enhances IL-15- and IL-2-induced proliferation via a CyA-sensitive pathway in this T-cell clone. In conclusion, the present data show that (i) SEA selectively inhibits IL-15- (but not PMA-) mediated proliferation in SEA "responder" T cells, (ii) SEA enhances cytokine-driven growth in psoriasis T cells with a "non-responder" phenotype, and (iii) crosstalk between SEA receptors and the IL-15R (and IL-2R) pathway is mediated via a PP2B-dependent and PP1/PP2A-, PKC-, PI-3 kinase- and mTOR-independent pathway in human T-cell lines.

M3 - Journal article

C2 - 9510372

VL - 51

SP - 164

EP - 173

JO - HLA

JF - HLA

SN - 2059-2302

IS - 2

ER -