LACK OF PROLIFERATIVE RESPONSE BY GLUTEN-SPECIFIC T-CELLS IN THE BLOOD AND GUT OF PATIENTS WITH DERMATITIS-HERPETIFORMIS

The majority of patients with Dermatitis Herpetiformis (DH) have a glu ten-sensitive enteropathy which may be triggered by a T cell-mediated immune response to gluten. Using a proliferative assay, the responses to gluten fraction III, recall antigens and mitogens of peripheral blo od mononuclear cells (PBMC) and gut T cell lines (TCL) isolated from p atients with Dermatitis Herpetiformis (DH) and normal controls were st udied. In most cases, neither PBMC nor gut T cell lines (which were pr edominantly CD3(+), CD4(+), TCR alpha beta(+)) from either controls or patients proliferated in response to gluten fraction III alone. Howev er, the addition of 10 U/ml IL-2 to PBMC cultures containing gluten fr action III resulted in a marked increase in proliferation in 9/19 DH p atients and 7/11 controls compared to IL-2 alone. Furthermore, gluten- induced upregulation of IL-2 receptor (CD25) expression was demonstrat ed on PBMC from 4/4 patients with DH and 2/3 controls after 7 days' cu lture with antigen. A similar effect by exogenous IL-2, or the same co ncentration of IL-4, was observed in 8/11 (P=0.02) and 5/6 respectivel y DH, and 3/4 normal gut T cell, lines. No difference was observed in the response of DH and control PBMC to Tetanus toxin, Candida albicans and PPD; both normal and DH gut T cell lines were unresponsive to the se antigens. However, the addition of IL-2 increased the response to C andida albicans by DH gut T cell lines. Moreover, the response of DH g ut T cell lines to PHA (P<0.001), Concanavalin A and anti-CD3 were mar kedly reduced compared to PBMC from the same patients. These findings suggest that gluten-specific T cells present in the blood and gut of n ormal and DH individuals are activated by but do not proliferate in re sponse to specific antigen. (C) 1995 Academic Press Limited