NADPH DIAPHORASE-POSITIVE DENDRITIC PROFILES IN RAT THYMUS ARE DISCRETE FROM AUTOFLUORESCENT CELLS, IMMUNOREACTIVE FOR INDUCIBLE NITRIC-OXIDE SYNTHASE, AND SHOW STRAIN-SPECIFIC ABUNDANCE DIFFERENCES

Predisposition to autoimmune disorder in Lewis rats has been associate d with abnormal hypothalamic regulation of circulating steroids, leadi ng to inadequate suppression of T helper 1 (Th1) cell-mediated inflamm atory reactions. In addition, autoimmune syndromes can be triggered wi thin formerly resistant animals, following damage to the negative sele ction process of the thymus. A contribution to the autoimmune-suscepti ble phenotype may therefore derive from the status of thymic tolerance . One mechanism of intrathymic negative selection may involve nitric o xide. Because inducible nitric oxide synthase (iNOS) is known to be in hibitable by steroids, its expression might be different within strain s having neuroendocrine disturbance. We report on a study to compare i ntrathymic iNOS expression in autoimmune-prone Lewis rats with Other r esistant strains. Interdigitating cells (IDC), darkly stained for diap horase, were confirmed as immunoreactive for iNOS. They were located t owards the medullary side of an accumulation of unstained, but autoflu orescent cells (presumed to be macrophages) that circumscribes the cor ticomedullary zone. The role of iNOS(+) IDC in the apoptotic deletion of T cells has been suggested by other studies. Despite the blunted st eroidal condition reported for Lewis, nitrergic cell abundance was sho wn, by quantitative analysis of histochemical stain, to be on average approximately twofold lower compared with resistant strains (Fischer a nd Sprague-Dawley). This trend was evident in males and females, and c onfirmed by independent observers. We hypothesize that an intrathymic, iNOS-dependent mechanism may be important for the suppression of pote ntially autoreactive T-cell clones.