Recombinant human interleukin 10 suppresses gliadin dependent T cell activation in ex vivo cultured coeliac intestinal mucosa.
BACKGROUND
Enteropathy in coeliac disease (CD) is sustained by a gliadin specific Th1 response. Interleukin (IL)-10 can downregulate Th1 immune responses.


OBJECTIVE
We investigated the ability of recombinant human (rh) IL-10 to suppress gliadin induced Th1 response.


METHODS
IL-10 RNA transcripts were analysed by competitive reverse transcription-polymerase chain reaction in duodenal biopsies from untreated and treated CD patients, non-coeliac enteropathies (NCE), and controls. CD biopsies were cultured with a peptic-tryptic digest of gliadin with or without rhIL-10. The proportion of CD80+ and CD25+ cells in the lamina propria, epithelial expression of Fas, intraepithelial infiltration of CD3+ cells, as well as cytokine synthesis (interferon gamma (IFN-gamma) and IL-2) were measured. Short term T cell lines (TCLs) obtained from treated CD biopsies cultured with gliadin with or without rhIL-10 were analysed by ELISPOT for gliadin specific production of IFN-gamma.


RESULTS
In untreated CD and NCE, IL-10 RNA transcripts were significantly upregulated. In ex vivo organ cultures, rhIL-10 downregulated gliadin induced cytokine synthesis, inhibited intraepithelial migration of CD3+ cells, and reduced the proportion of lamina propria CD25+ and CD80+ cells whereas it did not interfere with epithelial Fas expression. In short term TCLs, rhIL-10 abrogated the IFN-gamma response to gliadin.


CONCLUSIONS
rhIL-10 suppresses gliadin specific T cell activation. It may interfere with the antigen presenting capacity of lamina propria mononuclear cells as it reduces the expression of CD80. Interestingly, rhIL-10 also induces a long term hyporesponsiveness of gliadin specific mucosal T cells. These results offer new perspectives for therapeutic strategies in coeliac patients based on immune modulation by IL-10.
Salvati
V M
VM
Department of Paediatrics, University Federico II, Via Pansini, No 5, 80131 Naples, Italy.
Mazzarella
G
G
Gianfrani
C
C
Levings
M K
MK
Stefanile
R
R
De Giulio
B
B
Iaquinto
G
G
Giardullo
N
N
Auricchio
S
S
Roncarolo
M G
MG
Troncone
R
R
D000293:Adolescent; D000328:Adult; D002446:Celiac Disease / Q000178:diet therapy / Q000276:immunology*; D002460:Cell Line; D002648:Child; D002675:Child, Preschool; D005786:Gene Expression Regulation / Q000276:immunology; D005903:Gliadin / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D007223:Infant; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D016753:Interleukin-10 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D007413:Intestinal Mucosa / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008875:Middle Aged; D009924:Organ Culture Techniques; D012333:RNA, Messenger / Q000235:genetics; D011994:Recombinant Proteins / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D016176:T-Lymphocyte Subsets / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*
D012333:RNA, Messenger; D011994:Recombinant Proteins; D016753:Interleukin-10; D007371:Interferon-gamma; D005903:Gliadin