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Expression of 4-1BB and 4-1BBL in thymocytes during thymus regeneration.
Exp Mol Med. 2009 Dec 31; 41(12):896-911.EM

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 CD4(lo)CD8(lo), CD4(+)CD8(lo) and CD4(lo)CD8(+) 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 TCR(hi/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.

Authors+Show Affiliations

Department of Pediatrics, Pusan National University School of Medicine, Yangsan 626-870, Korea.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19745604

Citation

Kim, Young-Mi, et al. "Expression of 4-1BB and 4-1BBL in Thymocytes During Thymus Regeneration." Experimental & Molecular Medicine, vol. 41, no. 12, 2009, pp. 896-911.
Kim YM, Kim HK, Kim HJ, et al. Expression of 4-1BB and 4-1BBL in thymocytes during thymus regeneration. Exp Mol Med. 2009;41(12):896-911.
Kim, Y. M., Kim, H. K., Kim, H. J., Lee, H. W., Ju, S. A., Choi, B. K., Kwon, B. S., Kim, B. S., Kim, J. B., Lim, Y. T., & Yoon, S. (2009). Expression of 4-1BB and 4-1BBL in thymocytes during thymus regeneration. Experimental & Molecular Medicine, 41(12), 896-911. https://doi.org/10.3858/emm.2009.41.12.095
Kim YM, et al. Expression of 4-1BB and 4-1BBL in Thymocytes During Thymus Regeneration. Exp Mol Med. 2009 Dec 31;41(12):896-911. PubMed PMID: 19745604.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Expression of 4-1BB and 4-1BBL in thymocytes during thymus regeneration. AU - Kim,Young-Mi, AU - Kim,Hye Kyung, AU - Kim,Hyo Jin, AU - Lee,Hee-Woo, AU - Ju,Seong-A, AU - Choi,Beom K, AU - Kwon,Byoung S, AU - Kim,Bong-Seon, AU - Kim,Jae-Bong, AU - Lim,Young-Tak, AU - Yoon,Sik, PY - 2009/9/12/entrez PY - 2009/9/12/pubmed PY - 2010/3/24/medline SP - 896 EP - 911 JF - Experimental & molecular medicine JO - Exp Mol Med VL - 41 IS - 12 N2 - 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 CD4(lo)CD8(lo), CD4(+)CD8(lo) and CD4(lo)CD8(+) 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 TCR(hi/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. SN - 2092-6413 UR - https://www.unboundmedicine.com/medline/citation/19745604/Expression_of_4_1BB_and_4_1BBL_in_thymocytes_during_thymus_regeneration_ L2 - https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19745604/ DB - PRIME DP - Unbound Medicine ER -