BACKGROUND: Exposure of atopic patients to a specific allergen evokes an immediate response which is followed, in many cases, by a late phase reaction (LPR) some hours later. Here we have examined the immunological mechanisms required for the expression of cutaneous LPR in mice. METHODS: BALB/c mice were immunized by i.p. injection of ovalbumin (OVA) and alum actively or by i.v. injection of anti-OVA IgE monoclonal antibody (mAb) passively. After challenge by intradermal injection of OVA into ears, the changes in ear thickness, the number of eosinophils, and the levels of IL-4 and IFN-gamma protein at the site of antigen challenge were examined. RESULTS: Actively immunized mice developed a biphasic response at the site of OVA injection, while mice passively immunized with IgE anti-OVA mAb displayed a strong early response but no LPR. Cell transfer experiments using BALB/c nu/nu mice revealed that both OVA-specific IgE mAb and OVA-primed CD4 T cells were required to evoke LPR. Moreover, LPR was associated with increased levels of IL-4 production concomitant with reduced IFN-gamma production and was abolished by pretreatment with anti-IL-4 neutralizing mAb. CONCLUSION: It is suggested that murine cutaneous LPR against OVA is a type 2 inflammatory response in which both IgE antibodies and CD4 T cells play an obligatory role.
BACKGROUND: Exposure of atopic patients to a specific allergen evokes an immediate response which is followed, in many cases, by a late phase reaction (LPR) some hours later. Here we have examined the immunological mechanisms required for the expression of cutaneous LPR in mice. METHODS: BALB/c mice were immunized by i.p. injection of ovalbumin (OVA) and alum actively or by i.v. injection of anti-OVA IgE monoclonal antibody (mAb) passively. After challenge by intradermal injection of OVA into ears, the changes in ear thickness, the number of eosinophils, and the levels of IL-4 and IFN-gamma protein at the site of antigen challenge were examined. RESULTS: Actively immunized mice developed a biphasic response at the site of OVA injection, while mice passively immunized with IgE anti-OVA mAb displayed a strong early response but no LPR. Cell transfer experiments using BALB/c nu/nu mice revealed that both OVA-specific IgE mAb and OVA-primed CD4 T cells were required to evoke LPR. Moreover, LPR was associated with increased levels of IL-4 production concomitant with reduced IFN-gamma production and was abolished by pretreatment with anti-IL-4 neutralizing mAb. CONCLUSION: It is suggested that murine cutaneous LPR against OVA is a type 2 inflammatory response in which both IgE antibodies and CD4 T cells play an obligatory role.
Authors: Weilie Ma; Paul J Bryce; Alison A Humbles; Dhafer Laouini; Ali Yalcindag; Harri Alenius; Daniel S Friend; Hans C Oettgen; Craig Gerard; Raif S Geha Journal: J Clin Invest Date: 2002-03 Impact factor: 14.808