Intensive generation of NK1.1- extrathymic T cells in the liver by injection of bone marrow cells isolated from mice with a mutation of polymorphic major histocompatibility complex antigens

Whether intermediate TCR (TCRint) cells and natural killer T (NKT or NK1.1(+)TCR(int)) cells are extrathymically generated remains controversial. This arises from the fact that there are few of these T cells in the athymic nude mice and neonatally thymectomized mice. However, when athymic mice were provided with appropriate microenvironments or stimulation, many TCRint cells (mainly NK1.1(-)) were found to arise in the liver. NKT cells are known to be positively selected by monomorphic major histocompatibility complex (MHD)-like antigens (e.g. CD1d). This is true even if they are CD4(+). In other words, a MHC class 1-like antigen is restricted to CD4 antigen. This rule is somewhat different from that seen in conventional T cells (i.e., the restriction of class II with CD4 and that of class I and CD8). In the case of NK1.1(-)TCR(int) cells, they were selected by polymorphic MHC antigens, but their MHC restriction to CD4 or CD8 antigen was incomplete. This was revealed by experiments of bone marrow transfer with class I (bm 1) or II (bm 12) disparity. Depending on the disparity, a unique cytokine profile in sera was detected. These results suggest that the development of T lineage lymphocytes and MHC restriction to CD4 and CD8 might have occurred in parallel as a phylogenic event, and that NK1.1(-) extrathymic T cells (i.e., NK1.1(-)TCR(int)) are at an intermediate position between NKT cells and conventional T cells in phylogeny.