Bone marrow-derived cells fail to induce positive selection in thymus reaggregation cultures

The requirements for inducing positive selection of T cells were examined in thymus reaggregation cultures, a system in which dispersed populations of immature CD4(+) 8(+) cells and purified thymic epithelial cells (TEC) are reaggregated in tissue culture. Studies with TEC from mice selectively lacking major histocompatibility complex (MHC) class I (I-II+), class II (I+II-), or both class I and II (I-II-) molecules showed that class II expression was essential for the differentiation of CD4(+)8(+) cells into CD4(+)8(-) cells. Unexpectedly, the generation of TCR(hi) CD4(-)8(+) cells from CD4(+)8(+) cells was apparent with I-II+ TEC but not with I(-)II(-)TEC, perhaps reflecting cross-reactive specificity of CD4(-)8(+) cells for class II molecules. Significantly, the failure of I-II- TEC to generate TCR(hi) CD4(+)8(-) or CD4(-)8(+) cells could not be overcome by adding MHC(+) bone marrow-derived cells. These findings, together with experiments on purified subsets of TEC, suggest that positive selection in thymus reaggregation cultures is an exclusive property of cortical TEC.