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Peripheral CD4+ T cell cytokine responses following human challenge and re-challenge with Campylobacter jejuni.

Fimlaid KA, Lindow JC, Tribble DR, Bunn JY, Maue AC, Kirkpatrick BD - PLoS ONE (2014)

Bottom Line: A previous human challenge model has shown that C. jejuni elicits IFNγ production by peripheral blood mononuclear cells, a response associated with protection from clinical disease following re-infection.We show that CD4+ T cells make IFNγ and other pro-inflammatory cytokines in response to infection; however, multifunctional cytokine response patterns were not found.Cytokine production from peripheral CD4+ T cells was not enhanced following re-challenge, which may suggest deletion or tolerance.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Molecular Genetics, University of Vermont, Burlington, Vermont, 05405, United States of America; University of Vermont College of Medicine, Vaccine Testing Center and Unit of Infectious Diseases, Burlington, Vermont, United States of America.

ABSTRACT
Campylobacter jejuni is a leading cause of human gastroenteritis worldwide; however, our understanding of the human immune response to C. jejuni infection is limited. A previous human challenge model has shown that C. jejuni elicits IFNγ production by peripheral blood mononuclear cells, a response associated with protection from clinical disease following re-infection. In this study, we investigate T lymphocyte profiles associated with campylobacteriosis using specimens from a new human challenge model in which C. jejuni-naïve subjects were challenged and re-challenged with C. jejuni CG8421. Multiparameter flow cytometry was used to investigate T lymphocytes as a source of cytokines, including IFNγ, and to identify cytokine patterns associated with either campylobacteriosis or protection from disease. Unexpectedly, all but one subject evaluated re-experienced campylobacteriosis after re-challenge. We show that CD4+ T cells make IFNγ and other pro-inflammatory cytokines in response to infection; however, multifunctional cytokine response patterns were not found. Cytokine production from peripheral CD4+ T cells was not enhanced following re-challenge, which may suggest deletion or tolerance. Evaluation of alternative paradigms or models is needed to better understand the immune components of protection from campylobacteriosis.

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CD4+ T cell responses did not show a specific signature following re-challenge with the homologous C. jejuni strain.The effect of challenge on C. jejuni veterans shows a diverse T cell profile compared to naïve subjects. Eight subjects were re-dosed with the homologous C. jejuni CG8421 strain three months after initial infection. We examined CD4+ T cell responses for the production of IFNγ+, TNFα+, IL-2+, and MIP-1β at multiple timepoints pre- and post-re-infection. Responses shown are the percentage of cytokine positive CD4+ T cells from CAg-stimulated PBMCs with the background percentage of cytokine-positive T cells in the negative control (PBS) subtracted. D98 represents PBMCs from a blood drawn prior to re-infection. Bars represent percent of CD4+ T cells detected on specific days: D98 (day of re-dosing, yellow); D105 (blue); D112 (red); and D126 (black). No significant changes were observed post re-challenge compared to D98.
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pone-0112513-g002: CD4+ T cell responses did not show a specific signature following re-challenge with the homologous C. jejuni strain.The effect of challenge on C. jejuni veterans shows a diverse T cell profile compared to naïve subjects. Eight subjects were re-dosed with the homologous C. jejuni CG8421 strain three months after initial infection. We examined CD4+ T cell responses for the production of IFNγ+, TNFα+, IL-2+, and MIP-1β at multiple timepoints pre- and post-re-infection. Responses shown are the percentage of cytokine positive CD4+ T cells from CAg-stimulated PBMCs with the background percentage of cytokine-positive T cells in the negative control (PBS) subtracted. D98 represents PBMCs from a blood drawn prior to re-infection. Bars represent percent of CD4+ T cells detected on specific days: D98 (day of re-dosing, yellow); D105 (blue); D112 (red); and D126 (black). No significant changes were observed post re-challenge compared to D98.

Mentions: To evaluate whether an enhanced T cell response occurred following homologous re-infection, suggestive of activation of a memory T cell response, we analyzed responses following re-exposure to C. jejuni. Analysis of the cytokine kinetics post re-exposure in subjects that did not have protection from clinical disease showed variable responses compared to what was seen after first exposure (Fig. 2A-D); PBMCs were not available for all subjects on all days during the re-challenge denoted by a missing square from the figure plane. Overall, the cytokine responses at time-points following re-challenge were not significantly different relative to day of re-challenge (D98) or D0 for any of the cytokines under investigation.


Peripheral CD4+ T cell cytokine responses following human challenge and re-challenge with Campylobacter jejuni.

Fimlaid KA, Lindow JC, Tribble DR, Bunn JY, Maue AC, Kirkpatrick BD - PLoS ONE (2014)

CD4+ T cell responses did not show a specific signature following re-challenge with the homologous C. jejuni strain.The effect of challenge on C. jejuni veterans shows a diverse T cell profile compared to naïve subjects. Eight subjects were re-dosed with the homologous C. jejuni CG8421 strain three months after initial infection. We examined CD4+ T cell responses for the production of IFNγ+, TNFα+, IL-2+, and MIP-1β at multiple timepoints pre- and post-re-infection. Responses shown are the percentage of cytokine positive CD4+ T cells from CAg-stimulated PBMCs with the background percentage of cytokine-positive T cells in the negative control (PBS) subtracted. D98 represents PBMCs from a blood drawn prior to re-infection. Bars represent percent of CD4+ T cells detected on specific days: D98 (day of re-dosing, yellow); D105 (blue); D112 (red); and D126 (black). No significant changes were observed post re-challenge compared to D98.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4232357&req=5

pone-0112513-g002: CD4+ T cell responses did not show a specific signature following re-challenge with the homologous C. jejuni strain.The effect of challenge on C. jejuni veterans shows a diverse T cell profile compared to naïve subjects. Eight subjects were re-dosed with the homologous C. jejuni CG8421 strain three months after initial infection. We examined CD4+ T cell responses for the production of IFNγ+, TNFα+, IL-2+, and MIP-1β at multiple timepoints pre- and post-re-infection. Responses shown are the percentage of cytokine positive CD4+ T cells from CAg-stimulated PBMCs with the background percentage of cytokine-positive T cells in the negative control (PBS) subtracted. D98 represents PBMCs from a blood drawn prior to re-infection. Bars represent percent of CD4+ T cells detected on specific days: D98 (day of re-dosing, yellow); D105 (blue); D112 (red); and D126 (black). No significant changes were observed post re-challenge compared to D98.
Mentions: To evaluate whether an enhanced T cell response occurred following homologous re-infection, suggestive of activation of a memory T cell response, we analyzed responses following re-exposure to C. jejuni. Analysis of the cytokine kinetics post re-exposure in subjects that did not have protection from clinical disease showed variable responses compared to what was seen after first exposure (Fig. 2A-D); PBMCs were not available for all subjects on all days during the re-challenge denoted by a missing square from the figure plane. Overall, the cytokine responses at time-points following re-challenge were not significantly different relative to day of re-challenge (D98) or D0 for any of the cytokines under investigation.

Bottom Line: A previous human challenge model has shown that C. jejuni elicits IFNγ production by peripheral blood mononuclear cells, a response associated with protection from clinical disease following re-infection.We show that CD4+ T cells make IFNγ and other pro-inflammatory cytokines in response to infection; however, multifunctional cytokine response patterns were not found.Cytokine production from peripheral CD4+ T cells was not enhanced following re-challenge, which may suggest deletion or tolerance.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Molecular Genetics, University of Vermont, Burlington, Vermont, 05405, United States of America; University of Vermont College of Medicine, Vaccine Testing Center and Unit of Infectious Diseases, Burlington, Vermont, United States of America.

ABSTRACT
Campylobacter jejuni is a leading cause of human gastroenteritis worldwide; however, our understanding of the human immune response to C. jejuni infection is limited. A previous human challenge model has shown that C. jejuni elicits IFNγ production by peripheral blood mononuclear cells, a response associated with protection from clinical disease following re-infection. In this study, we investigate T lymphocyte profiles associated with campylobacteriosis using specimens from a new human challenge model in which C. jejuni-naïve subjects were challenged and re-challenged with C. jejuni CG8421. Multiparameter flow cytometry was used to investigate T lymphocytes as a source of cytokines, including IFNγ, and to identify cytokine patterns associated with either campylobacteriosis or protection from disease. Unexpectedly, all but one subject evaluated re-experienced campylobacteriosis after re-challenge. We show that CD4+ T cells make IFNγ and other pro-inflammatory cytokines in response to infection; however, multifunctional cytokine response patterns were not found. Cytokine production from peripheral CD4+ T cells was not enhanced following re-challenge, which may suggest deletion or tolerance. Evaluation of alternative paradigms or models is needed to better understand the immune components of protection from campylobacteriosis.

Show MeSH
Related in: MedlinePlus