J. Dekoning et al., THYMIC CORTICAL EPITHELIUM IS SUFFICIENT FOR THE DEVELOPMENT OF MATURE T-CELLS IN RELB-DEFICIENT MICE, The Journal of immunology, 158(6), 1997, pp. 2558-2566
Thymic development of T lymphocytes progresses as a consequence of bot
h TCR-mediated and non-TCR-mediated interactions between thymocytes an
d stromal cells. As relB-deficient mice appear to lack thymic medullar
y epithelium and mature dendritic cells, we studied the effect of this
''cortex-only'' thymus on T cell development. Two major consequences
were observed. First, in both relB mutant and TCR transgenic/relB muta
nt mice, positive selection of both TCR alpha beta and gamma delta T c
ells appeared to proceed normally, with export of fully functional T c
ells to the periphery, suggesting that the thymic medullary stromal ce
lls are not required for full maturation of T cells nor is an organize
d medullary compartment required for accumulation of mature single pos
itive CD4 and CD8 T cells. Second, thymic negative selection was impai
red, as evidenced by significant autoreactive proliferative responses
to normal spleen stimulators. Peripheral T cells in relB mutant mice s
howed an unusually high proportion of CD69(+) and CD44(high) cells. Wh
ile some of these cells may be autoreactive T cells, most of the cells
appeared to be activated by cytokines produced by relB mutant nonlymp
hoid cells, as the effect is minimized in relB mutant bone marrow chim
eras. In sum, while the TCR-mediated steps in T cell maturation requir
e both thymic cortex and medulla (epithelium and dendritic cells) for
normal positive and negative selection of the repertoire, non-TCR-medi
ated interactions in the thymic cortex alone are sufficient to generat
e mature functional T cells.