CONSTITUTIVELY DECREASED TH3 SUPPRESSOR CELLS MAY ALLOW LOW-DOSE SENSITISATION IN CMSE

Abstract

82 Aims: Many infants sensitise to dietary antigens despite exclusive breast feeding. While acknowledged an increasingly common cause of cows' milk sensitive enteropathy (CMSE), multiple food intolerances are now recognized 1,2. A defect in oral tolerance in atopic infants, specifically for low dose antigen and due to impaired generation of TH3 cells (TGF-β secreting T cells) has been postulated as a potential cause 3. We have thus studied mucosal TH1, TH2 and TH3 cells in CMSE and other enteropathies. Methods: Spontaneous production of IL-2, IFN-γ (TH1), IL-4 (TH2) and TGF-β (TH3) was analysed by flow cytometry (FACS) in the intraepithelial (IEL) and lamina propria (LPL) lymphocytes from 54 children with normal histology (n=17), active (16) and treated (9) CMSE, coeliac disease (7) or inflammatory enteropathy (5). Results: In contrast to coeliac disease and inflammatory enteropathy, active CMSE was characterised by reduced TH1 cytokine production. CD4+ IEL showed reduced IFNγ and TGFβ in CMSE at diagnosis, not seen on cows' milk exclusion. CD4+ LPL showed reduced IL-2 and IFNγ positive cells, again only in active disease. CD8+ IEL's and LPL's showed similar reduction of TH1 cytokines in active CMSE. However a striking decrease in TGFβ+ CD8+ IELs and LPLs was also seen, not only in active disease but persisting on cow's milk exclusion. Conclusions: We have found evidence of reduced TGFβ production by mucosal CD8+ cells in active CMSE and following cow's milk exclusion. CD4+ cells also show reduced TGFβ production, but only in active disease. Impaired generation of TH3 cells may thus be a predisposing factor for the development of CMSE. These finding are consistent with the hypothesis of impaired low-dose oral tolerance in atopic infants 3.