Aberrant expression of class II HLA antigens by the target cell: cause or consequence of the autoimmune aggression?

Abstract

Since the aberrant HLA-DR expression on thyroid follicular cells (TFC) has been found in glands already having an ongoing immune response, the possibility exists that this ectopic expression is not the primary event leading to the infiltration by autoreactive lymphocytes, but rather a consequence of that infiltration. We have explored that possibility in studies on the behaviour of TFC from normal and autoimmune glands with respect to their expression of HLA-DR antigens when they are cultured with or without autologous mononuclear cells from the intrathyroidal infiltrates or peripheral blood. Our findings suggest that 1) the ectopic expression of class II HLA antigens by TFC in autoimmune conditions is not the result of a primary or intrinsic defect of those cells but a consequence of their response to an environmental stimulus operating in situ; 2) this stimulus appears to be the lymphoid infiltration itself; 3) there are no significant differences in the responses given by TFC from autoimmune and normal glands. In alopecia areata, another presumably autoimmune condition characterized by the presence of lymphoid infiltration precedes that ectopic HLA-DR expression in vivo. In addition, we have found that human adrenocortical cells in the zona reticularis of adult glands normally express HLA-DR antigenic determinants. Therefore, the co-existence of both HLA-DR and potentially autoantigenic cell-surface constituents does not seem to be a sufficient stimulus to trigger an organ-specific autoimmune response.