Adrenocortical cells of the zona reticularis normally express HLA-DR antigenic determinants

A distinct population of normal human adrenocortical cells from adult glands spontaneously express HLA-DR, and occasionally also HLA-DQ, antigenic determinants in vivo and in vitro, as detected by immunofluorescence techniques using monoclonal antibodies on frozen tissue sections, primary cultures, and viable cell suspensions. In vivo, these antigenic determinants were found to be confined to the compact-type cells in the zona reticularis. In vitro, the adrenocortical identity of these HLA-DR+ cells was conclusively established by the characteristic change in their morphologic features induced by ACTH1-24 and by the simultaneous detection of tissue-specific adrenal autoantigens in double-label immunofluorescence staining. The cell surface expression of HLA-DR determinants by compact cells persisted in culture for several weeks and was not significantly affected by treatment with ACTH1-24. On the other hand, fetal adrenocortical cells of both transient and definitive zones were invariably negative for the expression of these HLA Class II antigenic determinants. Because normal human adrenocortical cells also express on their surface the molecules which constitute specific autoantigens in autoimmune adrenalitis, these findings argue against the notion that an ectopic HLA-DR expression associated with an otherwise "silent" autoantigen might trigger an organ-specific autoimmune response against endocrine cells. In addition, the expression of HLA-DR determinants by viable normal reticularis cells provides a readily detectable surface marker which may allow the physical separation of this population for studies in vitro.