Peripheral CD4⁺ T Cell Cytokine Responses Following Human Challenge and Re-Challenge with <i>Campylobacter jejuni</i>

<div><p><i>Campylobacter jejuni</i> is a leading cause of human gastroenteritis worldwide; however, our understanding of the human immune response to <i>C. jejuni</i> infection is limited. A previous human challenge model has shown that <i>C. jejuni</i> 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 <i>C. jejuni</i>-naïve subjects were challenged and re-challenged with <i>C. jejuni</i> 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.</p>