The Mitogenic Effect of the Lymphocytosis Promoting Factor from Bordetella Pertussis on Human Lymphocytes

Morse, Jane H.; Kong, A S; Lindenbaum, John; Morse, Stephen I.

doi:10.1172/jci108820

Cited by 38 publications

(15 citation statements)

References 18 publications

(23 reference statements)

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“…Its B-subunit binds to a receptor on the cell surface, and the enzymatically active A-subunit disrupts intracellular signaling by irreversible ADP ribosylation of the G i -subclass of G proteins (10,11). PT has pleiotropic effects on the immune system, such as T cell mitogenesis, augmentation of cytokine and Ab production, and the promotion of delayed type hypersensitivity responses (12)(13)(14)(15).…”

Section: E Xperimental Autoimmune Encephalomyelitis (Eae)mentioning

confidence: 99%

Pertussis Toxin Modulates the Immune Response to Neuroantigens Injected in Incomplete Freund’s Adjuvant: Induction of Th1 Cells and Experimental Autoimmune Encephalomyelitis in the Presence of High Frequencies of Th2 Cells

Hofstetter

Shive

Forsthuber

2002

The Journal of Immunology

143

110

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Pertussis toxin (PT) has been widely used to facilitate the induction of experimental autoimmune encephalomyelitis (EAE) in rodents. It has been suggested that this microbial product promotes EAE by opening up the blood-brain barrier and thereby facilitates the migration of pathogenic T cells to the CNS. However, PT has other biological effects that could contribute to its activity in EAE, such as enhancing the cytokine production by T cells and induction of lymphocytosis. In this work, we investigated the effects of PT on the pathogenicity, cytokine differentiation, and clonal sizes of neuroantigen-reactive T cells in EAE in mice. Our results show that PT prevented the protection from EAE conferred by injection of PLPp139–151 in IFA and induced high frequencies of peptide-specific Th1 cells and disease. Interestingly, the mice developed EAE despite the simultaneous vigorous clonal expansion of PLPp139–151-specific Th2 cells. The data indicate that the Th2 cells in this model neither were protective against EAE nor promoted the disease. Furthermore, the results suggested that the effects of the toxin on neuroantigen-reactive T cells were promoted by the PT-induced activation of APCs in lymphoid tissues and the CNS. Together, the results suggest that microbial products, such as PT, could contribute to the initiation of autoimmune disease by modulating the interaction between the innate and adaptive immune system in the response to self Ags.

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Section: E Xperimental Autoimmune Encephalomyelitis (Eae)mentioning

confidence: 99%

Pertussis Toxin Modulates the Immune Response to Neuroantigens Injected in Incomplete Freund’s Adjuvant: Induction of Th1 Cells and Experimental Autoimmune Encephalomyelitis in the Presence of High Frequencies of Th2 Cells

Hofstetter

Shive

Forsthuber

2002

The Journal of Immunology

143

110

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“…PTX has a wide range of biological effects including induction of leukocytosis, lymphocyte mitogenesis, enhancement of immunoglobulin IgG and IgE synthesis and strong adjuvant effects on antigen-specific T cell immunity promoting both Th1- and Th2-type inflammatory responses [3–8]. Of note, PTX is routinely used in experimental autoimmune disease models in animals, such as experimental autoimmune encephalomyelitis (EAE) in rodents, to promote the disease [9;10].…”

Section: Introductionmentioning

confidence: 99%

Induction of polyclonal CD8+ T cell activation and effector function by Pertussis toxin

Murphey

Chang

Zhang

et al. 2011

Cellular Immunology

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Pertussis toxin (PTX) has pronounced adjuvant activity and strongly enhances innate and adaptive immune responses, including increased antibody production and Th1/Th2 cytokine production. Adjuvant effects of PTX on Th1 and Th2 cells are primarily mediated via CD80/86 costimulation via enhanced expression of these molecules by APCs. However, it has remained unresolved whether PTX modulates the expression of costimulatory and inhibitory molecules on CD4+ and CD8+ T cells. To address this question, we determined the expression kinetics of CD28, CTLA-4, and CD40L on spleen CD4+ and CD8+ T cells after incubation with PTX. The results show that PTX upregulated the expression of CD28 by CD8+ T cells, but not by CD4+ T cells. In contrast, the expression of CTLA-4 and CD40L was not substantially altered on CD4+ or CD8+ T cells. CD28 upregulation by CD8+ T cells was paralleled by upregulation of CD69 and the induction of IFN-γ, Granzyme B (GrB), and IL-17. CD8+ T cell activation and cytokine production could be substantially blocked with anti-CD80 and CD86 antibodies, consistent with CD28 mediated signaling. Treatment of highly purified CD8+ T cells with PTX resulted in upregulation of CD28 and CD69, and production of IFN-γ. Incubation with CD28 mAb further enhanced this effect, suggesting that PTX has direct effects on CD8+ T cells which are enhanced by CD80/86-mediated costimulation provided by APCs.

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“…Like Zepp et al (39), we used detoxified PT for in vitro stimulation because native PT is known to display mitogenic activities on lymphocytes (22,25). Consequently, detection of specific responses using native antigens may be hampered by nonspecific T-cell proliferation due to the toxin.…”

Section: Discussionmentioning

confidence: 99%

Long-Term Pertussis-Specific Immunity after Primary Vaccination with a Combined Diphtheria, Tetanus, Tricomponent Acellular Pertussis, and Hepatitis B Vaccine in Comparison with That after Natural Infection

Esposito¹,

Agliardi²,

Giammanco³

et al. 2001

Infect Immun

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The aim of this study was to compare pertussis-specific humoral and cellular immunity in children 5 years after a primary vaccination with a combined diphtheria, tetanus, tricomponent acellular pertussis, and hepatitis B vaccine (DTaP-HBV; InfanrixHepB; SmithKline Beecham) with immunity after natural infection. The subjects were 38 children aged 5 to 6 years who received DTaP-HBV at 3, 5, and 11 months of life and 21 subjects of similar ages and sex who acquired pertussis in the first year of life. Immunoglobulin G (IgG) antibody titers against Bordetella pertussis antigens, peripheral blood mononuclear cell-specific proliferation, and the secretion of cytokines were evaluated. After 5 years, only a small proportion of vaccinated and infected children had significant specific concentrations of IgG in serum against all three B. pertussis antigens, and T-cell responses persisted in a minority of subjects. A preferential type 1 cytokine response with the secretion of gamma interferon was observed in the pertussis group, whereas a type 2 skewed response was observed in the vaccinated children; however, the quantitative differences in the cytokines produced by DTaP-HBV and natural infection were minimal. In conclusion, our results show that the immune responses induced by primary pertussis vaccination are qualitatively and quantitatively similar to those seen in children who recovered from natural infection and highlight the need for booster immunization with pertussis vaccines in order to maintain adequate levels of a specific immune response to B. pertussis.

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The Mitogenic Effect of the Lymphocytosis Promoting Factor from Bordetella Pertussis on Human Lymphocytes

Cited by 38 publications

References 18 publications

Pertussis Toxin Modulates the Immune Response to Neuroantigens Injected in Incomplete Freund’s Adjuvant: Induction of Th1 Cells and Experimental Autoimmune Encephalomyelitis in the Presence of High Frequencies of Th2 Cells

Pertussis Toxin Modulates the Immune Response to Neuroantigens Injected in Incomplete Freund’s Adjuvant: Induction of Th1 Cells and Experimental Autoimmune Encephalomyelitis in the Presence of High Frequencies of Th2 Cells

Induction of polyclonal CD8+ T cell activation and effector function by Pertussis toxin

Long-Term Pertussis-Specific Immunity after Primary Vaccination with a Combined Diphtheria, Tetanus, Tricomponent Acellular Pertussis, and Hepatitis B Vaccine in Comparison with That after Natural Infection

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