Expression of 4-1BB and 4-1BBL in thymocytes during thymus regeneration.
10.3858/emm.2009.41.12.095
- Author:
Young Mi KIM
1
;
Hye Kyung KIM
;
Hyo Jin KIM
;
Hee Woo LEE
;
Seong A JU
;
Beom K CHOI
;
Byoung S KWON
;
Bong Seon KIM
;
Jae Bong KIM
;
Young Tak LIM
;
Sik YOON
Author Information
1. Department of Pediatrics, Pusan National University School of Medicine, Yangsan 626-870, Korea.
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
4-1BB ligand;
antigens, CD137;
cell differentiation;
thymus gland;
T-lymphocytes
- MeSH:
4-1BB Ligand/genetics/*metabolism;
Animals;
Antigens, CD137/genetics/*metabolism;
CD4-Positive T-Lymphocytes/cytology/metabolism;
CD8-Positive T-Lymphocytes/cytology/metabolism;
Cell Adhesion;
Cell Differentiation;
Cell Line;
Cells, Cultured;
Cyclophosphamide/pharmacology;
Epithelial Cells/cytology;
Gene Expression Regulation;
Immunosuppressive Agents/pharmacology;
Male;
Mice;
Mice, Inbred C57BL;
RNA, Messenger/genetics;
*Regeneration;
T-Lymphocytes/*cytology/metabolism;
Thymus Gland/*cytology/drug effects/*physiology
- From:Experimental & Molecular Medicine
2009;41(12):896-911
- CountryRepublic of Korea
- Language:English
-
Abstract:
4-1BB, a member of the tumor necrosis factor receptor (TNFR) superfamily, is a major costimulatory receptor that is rapidly expressed on the surface of CD4+ and CD8+ T cells after antigen- or mitogen-induced activation. The interaction of 4-1BB with 4-1BBL regulates immunity and promotes the survival and expansion of activated T cells. In this study, the expression of 4-1BB and 4-1BBL was examined during regeneration of the murine thymus following acute cyclophosphamide-induced involution. Four-color flow cytometry showed that 4-1BB and 4-1BBL were present in the normal thymus and were preferentially expressed in the regenerating thymus, mainly in CD4+CD8+ double-positive (DP) thymocytes. Furthermore, the CD4loCD8lo, CD4+CD8lo and CD4loCD8+ thymocyte subsets, representing stages of thymocyte differentiation intermediate between DP and single-positive (SP) thymocytes, also expressed 4-1BB and 4-1BBL during thymus regeneration but to a lesser degree. Interestingly, the 4-1BB and 4-1BBL positive cells among the CD4+CD8+ DP thymocytes present during thymus regeneration were TCR(hi) and CD69+ unlike the corresponding controls. Moreover, the 4-1BB and 4-1BBL positive cells among the intermediate subsets present during thymus regeneration also exhibited TCRhi/int and CD69+/int phenotypes, indicating that 4-1BB and 4-1BBL are predominantly expressed by the positively selected population of the CD4+CD8+ DP and the intermediate thymocytes during thymus regeneration. RT-PCR and Western blot analyses confirmed the presence and elevated levels of 4-1BB and 4-1BBL mRNA and protein in thymocytes during thymus regeneration. We also found that the interaction of 4-1BB with 4-1BBL promoted thymocyte adhesion to thymic epithelial cells. Our results suggest that 4-1BB and 4-1BBL participate in T lymphopoiesis associated with positive selection during recovery from acute thymic involution.
