Blockage of T-cell costimulation inhibits T-cell action in celiac disease.
OBJECTIVE
Celiac disease is an exemplary model of T cell-mediated pathology. Therefore, therapeutic approaches that target T cells may successfully control this disease. CTLA-4 immunoglobulin (CTLA-4Ig) can inhibit T-cell activation by blocking the engagement of CD28. We took advantage of this tool to define the pathogenic role of gliadin-specific T cells in the induction of celiac disease.


METHODS
Duodenal biopsy specimens from 7 treated celiac patients were challenged in vitro with gliadin and CTLA-4Ig or CD40-Ig. After 24 hours, the biopsy specimens were analyzed for the presence of characteristic modifications induced by gliadin challenge.


RESULTS
CTLA-4Ig down-regulated the expression of CD25, intercellular adhesion molecule 1, interleukin 2, and interferon gamma (stained lamina propria mononuclear cells/mm2; P < 0.05) induced by gliadin challenge, caused apoptosis of gliadin-specific T cells (apoptotic T cells/mm2; P < 0.05), and inhibited the production of antiendomysial antibody (P < 0.01). However, it did not control intraepithelial T-cell migration (P = NS) and Fas expression by enterocytes. Conversely, CD40-Ig only controlled production of antiendomysial antibody.


CONCLUSIONS
In an organ culture model, CTLA-4Ig controls many but not all of the immunologic features of celiac disease.
Department of Pediatrics, University "Federico II," Naples, Italy.
L
L
Maiuri
S
S
Auricchio
S
S
Coletta
G
G
De Marco
A
A
Picarelli
M
M
Di Tola
S
S
Quaratino
M
M
Londei
D000069594:Abatacept; D015703:Antigens, CD / Q000276:immunology; D000943:Antigens, Differentiation / Q000276:immunology; D001706:Biopsy; D019013:CD40 Antigens / Q000276:immunology; D060908:CTLA-4 Antigen; D002446:Celiac Disease / Q000276:immunology* / Q000473:pathology; D002478:Cells, Cultured; D053938:DNA Fragmentation; D004386:Duodenum; D005903:Gliadin / Q000276:immunology*; D006801:Humans; D018796:Immunoconjugates; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D007413:Intestinal Mucosa / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology
D015703:Antigens, CD; D000943:Antigens, Differentiation; D019013:CD40 Antigens; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D018796:Immunoconjugates; D007376:Interleukin-2; D000069594:Abatacept; D007371:Interferon-gamma; D005903:Gliadin