| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Partners AIDS Research Center, Infectious Diseases Medicine, and Massachusetts General Hospital Cancer Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129
Developing thymocytes undergo maturation while migrating through the thymus and ultimately emigrate from the organ to populate peripheral lymphoid tissues. The process of thymic emigration is controlled in part via receptor-ligand interactions between the chemokine stromal-derived factor (SDF)-1, and its cognate receptor CXCR4, and sphingosine 1-phosphate (S1P) and its receptor S1PR. The precise mechanism by which S1P/S1PR and CXCR4/SDF-1 contribute to thymic emigration remains unclear. We proposed that S1P-dependent and -independent mechanisms might coexist and involve both S1P-induced chemoattraction and SDF-1-mediated chemorepulsion or fugetaxis of mature thymocytes. We examined thymocyte emigration in thymi from CXCR4-deficient C57BL/6 embryos in a modified assay, which allows the collection of CD62Lhigh and CD69low recent thymic emigrants. We demonstrated that single-positive (SP) CD4 thymocytes, with the characteristics of recent thymic emigrants, failed to move away from CXCR4-deficient fetal thymus in vitro. We found that the defect in SP CD4 cell emigration that occurred in the absence of CXCR4 signaling was only partially overcome by the addition of the extrathymic chemoattractant S1P and was not associated with abnormalities in thymocyte maturation and proliferative capacity or integrin expression. Blockade of the CXCR4 receptor in normal thymocytes by AMD3100 led to the retention of mature T cells in the thymus in vitro and in vivo. The addition of extrathymic SDF-1 inhibited emigration of wild-type SP cells out of the thymus by nullifying the chemokine gradient. SDF-1 was also shown to elicit a CXCR4-dependent chemorepellent response from fetal SP thymocytes. These novel findings support the thesis that the CXCR4-mediated chemorepellent activity of intrathymic SDF-1 contributes to SP thymocyte egress from the fetal thymus.
This article has been cited by other articles:
|
|
 |
|
  Y. Dong, X. Du, J. Ye, M. Han, T. Xu, Y. Zhuang, and W. Tao A Cell-Intrinsic Role for Mst1 in Regulating Thymocyte Egress J. Immunol., September 15, 2009; 183(6): 3865 - 3872. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Weinreich and K. A. Hogquist Thymic Emigration: When and How T Cells Leave Home J. Immunol., August 15, 2008; 181(4): 2265 - 2270. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. A. Mendes-da-Cruz, S. Smaniotto, A. C. Keller, M. Dardenne, and W. Savino Multivectorial Abnormal Cell Migration in the NOD Mouse Thymus J. Immunol., April 1, 2008; 180(7): 4639 - 4647. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. M. Stephenson, B. Sammut, D. B. Graham, J. Chan-Wang, K. L. Brim, A. S. Huett, A. V. Miletic, T. Kloeppel, A. Landry, R. Xavier, et al. DLGH1 Is a Negative Regulator of T-Lymphocyte Proliferation Mol. Cell. Biol., November 1, 2007; 27(21): 7574 - 7581. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Xu, A. Mora, H. Shim, A. Stecenko, K. L. Brigham, and M. Rojas Role of the SDF-1/CXCR4 Axis in the Pathogenesis of Lung Injury and Fibrosis Am. J. Respir. Cell Mol. Biol., September 1, 2007; 37(3): 291 - 299. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. P. Uldrich, S. P. Berzins, M. A. Malin, P. Bouillet, A. Strasser, M. J. Smyth, R. L. Boyd, and D. I. Godfrey Antigen challenge inhibits thymic emigration. J. Immunol., April 15, 2006; 176(8): 4553 - 4561. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Vianello, N. Papeta, T. Chen, P. Kraft, N. White, W. K. Hart, M. F. Kircher, E. Swart, S. Rhee, G. Palu, et al. Murine B16 Melanomas Expressing High Levels of the Chemokine Stromal-Derived Factor-1/CXCL12 Induce Tumor-Specific T Cell Chemorepulsion and Escape from Immune Control. J. Immunol., March 1, 2006; 176(5): 2902 - 2914. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
