The T-cell repertoire is shaped by the positive and negative selection of i
mmature CD4(+) CD8(+) double positive (DP) thymocytes. Positive selection o
f DP T cells to the CD4(+) CD8(-) and CD4(-) CD8(+) simple positive (SP) li
neages is a multistep process which involves cellular interactions between
thymocytes and stromal cells. Mutant nackt (nkt/nkt) mice have been shown t
o have a deficiency in the CD4(+) CD8(-) T-cell subset both in the thymus a
nd in the periphery. The present report suggests that nkt/nkt mice present
alterations in early steps of positive selection because they show decrease
s in the percentages of CD69(+) and CD5(+) cells within the DP subset. Expe
riments involving bone marrow transfer and thymic chimeras demonstrate that
the thymic epithelium of nkt/nkt mice is involved in the alterations regis
tered during positive selection and dictates the ultimate fate of CD4(+) SP
cells.