Expression of 4-1BB and 4-1BBL in thymocytes during thymus regeneration
Young-Mi KIM; 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.
Experimental & Molecular Medicine
; : 896-911, 2009.
Artículo
en Inglés
| WPRIM | ID: wpr-202557
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.
Asunto(s)
Animales Masculino Ratones Ligando 4-1BB/genética Miembro 9 de la Superfamilia de Receptores de Factores de Necrosis Tumoral/genética Linfocitos T CD4-Positivos/citología Linfocitos T CD8-positivos/citología Adhesión Celular Diferenciación Celular Línea Celular Células Cultivadas Ciclofosfamida/farmacología Células Epiteliales/citología Regulación de la Expresión Génica Inmunosupresores/farmacología Ratones Endogámicos C57BL ARN Mensajero/genética Regeneración Linfocitos T/citología Timo/citología
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