| Murine listeriosis makes an excellent model to study the regulation of the immune response as resolution of infection involves the fine coordination of innate and antigen-specific cells. By understanding how a successful immune responses work, we can begin to understand what happens when it does not work optimally.;Initially, the innate response to Listeria monocytogenes was characterized in C57BL/6 mice. Intraperitoneal infection resulted in an early systemic burst of proinflammatory cytokines. In the peritoneal cavity, mature macrophages were absent while neutrophils and immature macrophages were prevalent. Pre-infection frequencies of myeloid cells returned by day 10. In mice lacking gammadelta T cells (TCRd-/-), this response was profoundly altered. Systemic cytokines peaked at higher levels and remained elevated. In the peritoneal cavity, mature macrophages were absent until 2--3 weeks after infection, while frequencies of the neutrophils and immature macrophages were elevated and remained until day 10. In general, the innate inflammatory response was exaggerated and prolonged in mice lacking gammadelta T cells suggesting a role for gammadelta T cells in limiting inflammation and promoting macrophage maturation.;On day 10 post-infection peritoneal CD4+ T cells co-expressed three cytokines, TNFalpha, IFNgamma, and IL-2, after in vitro restimulation after polyclonal or listerial antigen stimulation, while splenocytes were predominantly TNFalpha+IFNgamma+. Stimulation of enriched T cells did not affect the pattern of cytokine expression and 24 h of infection was sufficient to elicit triple-positive CD4+ T cells. Triple cytokine expression by peritoneal CD4+ T cells was therefore a signature of programmed in vivo differentiation and activation. In mice lacking gammadelta T cells, these patterns were maintained, but the magnitude of the response increased. A higher frequency of cells expressed and secreted cytokines after polyclonal and dead Listeria stimulation; however, the response to a dominant epitope was diminished.;In the absence of gammadelta T cells during the immune response to Listeria, myeloid cells are compromised in their ability to focus the alphabeta T cell response to a dominant epitope, leading instead to the activation of alphabeta T cells with a broad spectrum of recognition. This data suggests that alterations in myeloid cells from TCRd-/- mice may affect the development of the antigen specific response and underlies the importance of gammadelta T cells in bridging the innate and adaptive immune response. |
