The effect of soluble LAG-3 (CD223) treatment in fetal thymic organ culture |
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Authors: | Taehoon Chun Hyun-Jung Byun Hee Yong Chung Yong-Hoon Chung |
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Affiliation: | Department of Microbiology and Immunology, School of Medicine, Hanyang University, Haeng-Dang Dong, Sung-Dong Ku, Seoul 133-791, South Korea. |
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Abstract: | 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. |
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Keywords: | co-receptor fetal thymic organ culture fusion protein lymphocyte activation gene-3 T cell precursor thymic selection |
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