Dual effects of pertussis toxin on lymphoid cells in culture

Vistica, Barbara P.; McAllister, Cathy G.; Sekura, Ronald D.; Ihle, James N.; Gery, Igal

doi:10.1016/0008-8749(86)90200-5

Cited by 32 publications

(16 citation statements)

References 30 publications

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“…By contrast, Vistica etai. (27) found that pertussis toxin could activate interleukin-1 production in primary mouse and human macrophage cell populations, but these eflFects required much higher concentrations (in the range of jig/mL) than used here.…”

Section: Discussionmentioning

confidence: 54%

Activation of macrophages to express cytocidal activity correlates with inhibition of their responsiveness to macrophage colony‐stimulating factor (CSF‐1): Involvement of a pertussis toxin‐sensitive reaction

Hume¹,

Denkins

1989

Immunol Cell Biol

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Summary Bone marrow-derived murine macrophages were used to study the relationship between the proliferative response of macrophages to macrophage colony-stimulating factor (CSF-1) and their activation for cytocidal activity against tumour cells. Macrophage activation required two sequential signals. Lymphokines (gamma intcrfcron, interleukin-4) provided the first (priming) signal; bacterial products (lipopolysaccharide. lipophilic muramyl tripeptidc, Mpopeptide 31362, pertussis toxin) provided the second (triggering) signal. Both priming and triggering agents inhibited ['H]-thymidine uptakeby macrophages stimulated with CSF-1. The antiproliferative activity of priming and triggering stimuli was synergislic, Pretreatment with triggering stimuli at 37°C caused a rapid reduction of the subsequent binding of ['^^IJ-CSE-I to the cell surface at 4°C. whereas priming agents had relatively little effect. Growth inhibitionby both priming and triggering agents was largely reversible by washing the cells, and occurred even when they were added as long as 24 h after the growth factor. The ability of pertussis toxin to both inhibit CSF-1-induced proliferation and trigger cytotoxicity in macrophages suggests the involvement of a regulatory GTP-binding protein (G protein) in both processes.

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Section: Discussionmentioning

confidence: 54%

Activation of macrophages to express cytocidal activity correlates with inhibition of their responsiveness to macrophage colony‐stimulating factor (CSF‐1): Involvement of a pertussis toxin‐sensitive reaction

Hume¹,

Denkins

1989

Immunol Cell Biol

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“…However, it has been reported that a high concentration of PTx itself stimulates IL-2 production [33], and we also observed that treatment with PTx (1 lg/mL) in vitro resulted in the release of IL-2 by mouse splenocytes (data not shown). This discrepancy may be the basis for the previously proposed dual effect of PTx: it activates mononuclear phagocytes and lymphocytes itself, while inhibiting the response of those immunocytes to other stimuli [37]. Although deprivation of IL-2 by PTx treatment is a very attractive explanation for the reduction of Treg activity, further research is needed to clarify exactly how PTx affects IL-2 production in vivo.…”

Section: Discussionmentioning

confidence: 97%

Pertussis toxin as an adjuvant suppresses the number and function of CD4⁺CD25⁺ T regulatory cells

et al. 2006

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We observed a remarkable reduction in the frequency and immunosuppressive activity of splenic CD4 + CD25 + T cells in C57BL/6 mice with MOG 33-55 -induced experimental autoimmune encephalomyelitis (EAE). Our study revealed that pertussis toxin (PTx), one component of the immunogen used to induce murine EAE, was responsible for down-regulating splenic CD4+ CD25 + cells. Treatment of normal BALB/c mice with PTx in vivo reduced the frequency, suppressive activity and FoxP3 expression by splenic CD4 + CD25 + T cells. However, PTx treatment did not alter the expression of characteristic phenotypic markers (CD45RB, CD103, GITR and CTLA-4) and did not increase the expression of CD44 and CD69 by the residual splenic and lymph node CD4 + CD25 + T cells. This property of PTx was attributable to its ADP-ribosyltransferase activity. PTx did not inhibit suppressive activity of purified CD4 + CD25 + T regulatory (Treg) cells in vitro, but did so in vivo, presumably due to an indirect effect. Although the exact molecular target of PTx that reduces Treg activity remains to be defined, our data suggests that alteration of both distribution and function of splenic immunocytes should play a role. This study concludes that an underlying cause for the immunological adjuvanticity of PTx is down-regulation of Treg cell number and function.

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“…6B). This discrepancy may be attributable to the reported dual actions of PTx (43) and the potential suppressive effects of IL-17 on the differentiation of Th1 cells.…”

Section: Discussionmentioning

confidence: 98%

Pertussis Toxin by Inducing IL-6 Promotes the Generation of IL-17-Producing CD4 Cells

Chen

Howard

Oppenheim

2007

The Journal of Immunology

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Compelling evidence has now demonstrated that IL-17-producing CD4 cells (Th17) are a major contributor to autoimmune pathogenesis, whereas CD4+CD25+ T regulatory cells (Treg) play a major role in suppression of autoimmunity. Differentiation of proinflammatory Th17 and immunosuppressive Treg from naive CD4 cells is reciprocally related and contingent upon the cytokine environment. We and others have reported that in vivo administration of pertussis toxin (PTx) reduces the number and function of mouse Treg. In this study, we have shown that supernatants from PTx-treated mouse splenic cells, which contained IL-6 and other proinflammatory cytokines, but not PTx itself, overcame the inhibition of proliferation seen in cocultures of Treg and CD4+CD25− T effector cells. This stimulatory effect could be mimicked by individual inflammatory cytokines such as IL-1β, IL-6, and TNF-α. The combination of these cytokines synergistically stimulated the proliferation of CD4+CD25− T effector cells despite the presence of Treg with a concomitant reduction in the percentage of FoxP3+ cells and generation of IL-17-expressing cells. PTx generated Th17 cells, while inhibiting the differentiation of FoxP+ cells, from naive CD4 cells when cocultured with bone marrow-derived dendritic cells from wild-type mice, but not from IL-6−/− mice. In vivo treatment with PTx induced IL-17-secreting cells in wild-type mice, but not in IL-6−/− mice. Thus, in addition to inhibiting the development of Treg, the immunoadjuvant activity of PTx can be attributable to the generation of IL-6-dependent IL-17-producing CD4 cells.

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Dual effects of pertussis toxin on lymphoid cells in culture

Cited by 32 publications

References 30 publications

Activation of macrophages to express cytocidal activity correlates with inhibition of their responsiveness to macrophage colony‐stimulating factor (CSF‐1): Involvement of a pertussis toxin‐sensitive reaction

Activation of macrophages to express cytocidal activity correlates with inhibition of their responsiveness to macrophage colony‐stimulating factor (CSF‐1): Involvement of a pertussis toxin‐sensitive reaction

Pertussis toxin as an adjuvant suppresses the number and function of CD4⁺CD25⁺ T regulatory cells

Pertussis Toxin by Inducing IL-6 Promotes the Generation of IL-17-Producing CD4 Cells

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Dual effects of pertussis toxin on lymphoid cells in culture

Cited by 32 publications

References 30 publications

Activation of macrophages to express cytocidal activity correlates with inhibition of their responsiveness to macrophage colony‐stimulating factor (CSF‐1): Involvement of a pertussis toxin‐sensitive reaction

Activation of macrophages to express cytocidal activity correlates with inhibition of their responsiveness to macrophage colony‐stimulating factor (CSF‐1): Involvement of a pertussis toxin‐sensitive reaction

Pertussis toxin as an adjuvant suppresses the number and function of CD4+CD25+ T regulatory cells

Pertussis Toxin by Inducing IL-6 Promotes the Generation of IL-17-Producing CD4 Cells

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Pertussis toxin as an adjuvant suppresses the number and function of CD4⁺CD25⁺ T regulatory cells