THYMIC MICROENVIRONMENTAL ABNORMALITIES IN MRL MP-LPR/LPR, BXSB/MPJ YAA AND C3H HEJ-GLD/GLD MICE/

Efforts to define the stromal architecture of thymic tissues of normal mice have used a panel of monoclonal antibodies (MTS series) to exami ne the localization of cell subtypes, including reagents that define t hymic epithelial and stromal elements. Recent work with these MTS mAbs disclosed significant abnormalities in the thymic cortex of New Zeala nd mice including the appearance of medullary type epithelial cells in the cortical areas and the presence of epithelial free spaces or 'cor tical holes'. To determine whether such abnormalities are unique to NZ B mice or are found in other models of murine lupus, we examined the t hymi of MRL/MP-lpr/lpr BXSB/MpJ Yaa, C3H/HeJ-gld/gld and C57BL/6 contr ol mice. Thymi from all models of murine lupus showed dramatic alterat ions in the thymic microarchitecture. For example, staining with MTS10 , a mAb which is specific for subcapsular and medullary epithelia, was decreased in the subcapsular and medullary regions, Moreover, there w as increased staining in the thymic cortex, suggesting an abnormality in the localization of MTS10-reactive cells. Moreover, all three murin e lupus strains demonstrated 'cortical holes' or cortical epithelial c ell-free regions. By using MTS33, MTS35 and flow cytometry, both C3H/g ld and BXSB/Yaa, but not MRL/lpr mice, showed decreased cortical thymo cyte frequencies. Possible defects in the maturation of double-positiv e thymocytes to single-positive status in C3H/gld mice is implied by a bnormally high levels of double-positive cells and low levels of singl e-positive cells. Finally, MRL/lpr thymocytes had lowered frequencies of CD3(-)4(+)8(+) and increased levels of TCR-alpha/beta(high) cells. Overall, these data suggest the need to define the functional implicat ions of the dramatic changes within the thymic cortex in murine lupus.