AbstractUsing mice deficient for LFA-1, CD44, and ICAM-1, we examined the role of these adhesion molecules in NK1.1+TCRαβ+ (NKT) cell development. Although no defect in NKT cell development was observed in CD44−/− and ICAM-1−/− mice, a dramatic reduction of liver NKT cells was observed in LFA-1−/− mice. Normal numbers of NKT cells were present in other lymphoid organs in LFA-1−/− mice. When LFA-1−/− splenocytes were injected i.v. into wild-type mice, the frequency of NKT cells among donor-derived cells in the recipient liver was normal. In contrast, when LFA-1−/− bone marrow (BM) cells were injected i.v. into irradiated wild-type mice, the frequency of liver NKT cells was significantly lower than that of mice injected with wild-type BM cells. Collectively, these data indicate that LFA-1 is required for the development of liver NKT cells, rather than the migration to and/or subsequent establishment of mature NKT cells in the liver.