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Cell Immunol ; 249(1): 8-19, 2007 Sep.
Article in English | MEDLINE | ID: mdl-18039542

ABSTRACT

Analysis of the NK cell developmental pathway suggests that CD2 expression may be important in regulating NK maturation. To test this hypothesis, we developed mice containing only an inhibitory CD2 molecule by linking the extracellular domain of CD2 to an intracellular immunoreceptor tyrosine-based inhibitory motif (ITIM) motif. Mice containing the CD2 Tg(ITIM) transgene, introduced into a CD2 KO background, have no morphologically detectable lymph nodes, although development of the thymus appears normal. In addition, these mice had major loss of both NK and NKT subsets in peripheral organs, while T and B cell frequencies were intact. Expression of CD2 was low on T cells and lacking on B cells and functional defects were observed in these populations. NKT cells expressing CD4 were absent, while the CD8+ and double negative NKT cells were retained. Small subsets of NK cells were detected but expression of CD2 on these cells was very low or absent, and their maturation was impaired. Based on the phenotype described here, we believe that these mice represent a unique model to study lymphoid organ and lymphocyte development.


Subject(s)
CD2 Antigens/immunology , Killer Cells, Natural/immunology , Lymphocyte Subsets/immunology , Thymus Gland/immunology , Animals , B-Lymphocytes/immunology , B-Lymphocytes/metabolism , CD2 Antigens/chemistry , CD2 Antigens/genetics , CD2 Antigens/metabolism , CD4 Antigens/metabolism , CD8 Antigens/metabolism , Cell Differentiation , Humans , Killer Cells, Natural/cytology , Lymphocyte Count , Lymphocyte Subsets/cytology , Mice , Mice, Inbred C57BL , Mice, Transgenic , Protein Structure, Tertiary , T-Lymphocytes/immunology , T-Lymphocytes/metabolism , Tyrosine
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