Abstract
Purpose:
Complete Freunds Adjuvant (CFA) is an oily emulsion with mycobacterial components that is used as an adjuvant to induce antigen-specific autoimmunity, such as experimental autoimmune uveitis (EAU). Our previous work demonstrated that CFA is also capable of non-specific activation of regulatory T cells (Treg). The purpose of the present study was to analyze the immunoregulatory properties of CFA in EAU.
Methods:
Wild-type (WT) and IL-10 knockout (KO) C57Bl/6 mice were pre-treated by subcutaneous injection of CFA or Incomplete Freunds Adjuvant (IFA) seven days before induction of EAU by immunization with IRBP peptide 1-20 emulsified in CFA and with Pertussis-Toxin (PTX). EAU scores (scale ranging in severity from 0= no disease to 4 = complete retinal destruction) and associated immunological responses (delayed type hypersensitivity, DTH) were examined.
Results:
Pre-treatment with CFA in WT mice (CFA/WT) significantly reduced incidence (p=0.049) and severity (p=0.005) of EAU compared to IFA pre-treatment (IFA/WT). Conversely, pre-treatment of KO mice with CFA (CFA/KO) did not alter incidence and severity of EAU, when compared to IFA pre-treatment of KO mice (IFA/KO). Comparably, the DTH response was significantly lower in the CFA/WT than in the IFA/WT group (p=0.016) and not significantly different in the CFA/KO versus the IFA/KO group. EAU scores and incidence, as well as DTH were not statistically different between the control groups of the two mouse strains (IFA/WT versus IFA/KO).
Conclusions:
Although CFA is needed to induce EAU, it partially also has immunosuppressive properties that may be utilized, when it is administered before immunization with antigen. This effect seems to represent an active immunosuppressive mechanism rather than being due to passive exhaustion of effector mechanisms, because it is dependent on the presence of IL-10.
Keywords: 746 uveitis-clinical/animal model •
432 autoimmune disease •
555 immunomodulation/immunoregulation