Y. Watanabe et al., THYMIC MICROENVIRONMENTAL ABNORMALITIES AND THYMIC SELECTION IN NZB.H-2(BM12) MICE, The Journal of immunology, 150(10), 1993, pp. 4702-4712
We have taken advantage of an extensive panel of mAb directed to thymi
c epithelial and nonepithelial stromal cells to examine the expression
of these Ag from day 16 of gestation through 6 mo of age in NZB(H-2d)
, NZB.H-2b, NZB.H-2bm12, C57BL/6(H-2b), and C57BL/6.H-2bm12 mice. In a
ddition, by triple color flow cytometry we have examined the expressio
n of cell surface markers defining distinct stages of intrathymic T ce
ll maturation. New Zealand mice demonstrated three abnormalities. MTS
10 normally stains thymic medullary and subcapsular epithelium. Howeve
r, New Zealand mice demonstrated striking irregular medullary epitheli
al cell shape whereas their subcapsular epithelium remained normal. Mo
reover, New Zealand mice, unlike controls, were found to have MTS 10epithelial cells within the cortex. Additionally, MTS 39 and MTS 44, w
hich normally stain reticular cortical epithelium, produced a striking
different staining pattern in New Zealand mouse thymus, including the
presence of large cortical epithelial cellfree regions, so-called ''c
ortical holes.'' MTS 33 normally stains cortical thymocytes but in New
Zealand mice, there was a severe decrease of MTS 33+ cells. There was
also an increase of CD3lowCD4+CD8+ cells in NZB mice, which may inclu
de many predeletion thymocytes. Finally, there was a significant incre
ase of CD3(high)CD4+CD8- cells in NZB.H-2bm12 and C57BL/6.H-2bm12 mice
compared with NZB.H-2b and C57BL/6(H-2b)mice. We postulate that these
microenvironmental alterations in NZB mice contribute to and reflect
altered T cell differentiation, thereby predisposing them to autoimmun
e disease. Moreover, the increased proportion of CD3(high)CD4+CD8- cel
ls associated with the H-2bm12 mutation may be involved in the remarka
bly different profiles of disease between NZB.H-2b and NZB.H-2bm12 mic
e.