Kinetics of IL-17- and interferon-γ-producing PLPp-specific CD4 T cells in EAE induced by coinjection of PLPp/IFA with pertussis toxin in SJL mice

Abstract

Systemic administration of Pertussis toxin (PTX) abrogates T cell tolerance mediated by injection of neuroantigens in incomplete Freund's adjuvant (IFA) and causes experimental autoimmune encephalomyelitis (EAE). PTX concomitantly induces high frequencies of neuroantigen-specific IFN-γ- and IL-17-producing T cells. Both IL-17 and IFN-γ have been implicated as a key effector cytokines in the pathogenesis of EAE, possibly with different functions. We therefore investigated potential differences in the temporal and spatial kinetics of the PTX-induced neuroantigen-specific IFN-γ- and IL-17-producing T cell effector populations. IFN-γ- and IL-17-producing PLPp-specific T cells initially arose in comparable frequencies in the local draining lymph nodes (drLN) after immunization as measured by cytokine ELISPOT. High frequencies of both IFN-γ- and IL-17-producing T cells were present in the immune periphery before onset of EAE. The highest frequencies of PTX-induced IFN-γ- and IL-17-producing PLPp-specific cells coincided in the inflamed CNS during acute EAE. During recovery, both IFN-γ- and IL-17-producing PLPp-specific T cells simultaneously disappeared from the CNS, whereas high frequencies of these cells remained present in the immune periphery. The functional affinity of both IFN-γ- and IL-17-producing T cells did not change during EAE. Therefore, autoimmune pathology in this model did not correlate with specific PTX effects either on Th1 or Th17 cells regarding their kinetics and CNS migration.