identification of cd4？cd8？ double-negative natural killer t cell precursors in the thymus识别cd4 cd8 双重否定自然杀伤t细胞胸腺的前兆.pdfVIP

Identification of CD42CD82 Double-Negative Natural Killer T Cell Precursors in the Thymus Nyambayar Dashtsoodol, Hiroshi Watarai, Sakura Sakata, Masaru Taniguchi* Laboratory for Immune Regulation, RIKEN Research Center for Allergy and Immunology, Tsurumi-ku, Yokohama, Kanagawa, Japan Abstract Background: It is well known that CD1d-restricted Va 14 invariant natural killer T (NKT) cells are derived from cells in the CD4+CD8+ double-positive (DP) population in the thymus. However, the developmental progression of NKT cells in the earlier stages remains unclear, and the possible existence of NKT cell presursors in the earlier stages than DP stage remains to be tested. Principal Findings: Here, we demonstrate that NKT cell precursors that express invariant Va 14-Ja 18 transcripts but devoid of surface expression of the invariant Va14 receptor are present in the late CD42CD82 double-negative (DN)4 stage and have the potential to generate mature NKT cells in both in vivo and in vitro experimental conditions. Moreover, the DN4 population in CD1d knock-out (CD1dKO) mice was similar to those with an NKT cell potential in wild-type (WT) C57BL/6 (B6) mice, but failed to develop into NKT cells in vitro. However, these precursors could develop into NKT cells when co-cultured with normal thymocytes or in an in vivo experimental setting, indicating that functional NKT cell precursors are present in CD1dKO mice. Conclusions: Together, these results demonstrate that thymic DN4 fraction contains NKT cell precursors. Our findings provide new insights into the early development of NKT cells prior to surface expression of the invariant Va14 antigen receptor and suggest the possible alternative developmental pathway of NKT cells. Citation: Dashtsoodol N, Watarai H, Sakata S, Taniguchi M (2008) Identification of CD42CD82 D