The effect of soluble LAG-3 (CD223) treatment in fetal thymic organ culture.
Lymphocyte activation gene-3 (LAG-3; CD223) is structurally similar to CD4 and binds to MHC class II with a 100-fold higher affinity than that of CD4. Soluble LAG-3 (sLAG-3Ig) might be useful for immunotherapy by inducing MHC class II-mediated cell activation. A new form of sLAG-3Ig was constructed containing a critical binding site (D1 and D2 region) to MHC class II, combined with a Fc portion of an immunoglobulin gamma1. After treatment of sLAG-3Ig in fetal thymic organ culture from DO11.10 transgenic mouse, CD4(+) T cell precursors were increased in the positive selection but not affected in the negative selection. Further analysis by treating sLAG-3Ig on thymic epithelial cells revealed that CD40 and MHC class II were up-regulated. These results may demonstrate that the treatment of sLAG-3Ig increases the precursor frequency of CD4(+) T cells by activation of thymic epithelial cells.
Chun
Taehoon
T
Department of Microbiology and Immunology, School of Medicine, Hanyang University, Haeng-Dang Dong, Sung-Dong Ku, Seoul 133-791, South Korea.
Byun
Hyun-Jung
HJ
Chung
Hee Yong
HY
Chung
Yong-Hoon
YH
D000818:Animals; D015703:Antigens, CD / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D019013:CD40 Antigens / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D004847:Epithelial Cells / Q000502:physiology*; D005333:Fetus; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D009924:Organ Culture Techniques; D011994:Recombinant Proteins / Q000494:pharmacology; D013950:Thymus Gland; D000093322:Lymphocyte Activation Gene 3 Protein
D015703:Antigens, CD; D019013:CD40 Antigens; D000949:Histocompatibility Antigens Class II; D011994:Recombinant Proteins; D000093322:Lymphocyte Activation Gene 3 Protein; C000720327:Lag3 protein, mouse