The Journal of Immunology, Vol 154, Issue 11 5862-5869, Copyright © 1995 by American Association of Immunologists

ARTICLES

Regulation of early T cell development by the engagement of TCR-beta complex expressed on fetal thymocytes from TCR-beta-transgenic scid mice

Y Takahama, K Sugaya, S Tsuda, T Hasegawa and Y Hashimoto
Institute of Immunology, Syntex, Ibaraki, Japan.

Transgenic expression of the beta-chain of T cell antigen-receptor (TCR) is known to induce the generation of CD4+ CD8+ thymocytes in the immunodeficient scid mouse, in which thymocyte development is otherwise arrested at CD4- CD8- cells. It is not clear, however, whether or not the thymocyte development is controlled by ligand engagement of the TCR- beta complex on the cell surface. In the present study, we have examined how the engagement by Ab of the TCR-beta complex expressed on the TCR-beta-transgenic scid fetal thymocytes can regulate the generation of CD4+ CD8+ thymocytes. Organ cultures of CD4- CD8- day 14 fetal thymocytes from the TCR-beta-transgenic scid mice resulted in the generation of CD4- CD8+ and then CD4+ CD8+ cells. The initial step from CD40- CD8- cells to CD4- CD8+ cells was enhanced by the addition of anti-TCR-beta Ab, whereas the subsequent step from CD4- CD8+ cells to CD4+ CD8+ cells was markedly inhibited by anti-TCR-beta Ab. These results indicate that ligand engagement of the TCR-beta complex can positively and negatively regulate the early thymocyte development. Moreover, the finding that engagement of TCR-beta complex inhibits the generation of CD4+ CD8+ cells suggests that the induction of CD4+ CD8+ thymocytes by the TCR-beta transgene is not an immediate consequence of cell-surface engagement of the TCR-beta complex but requires liberation from the continued TCR-beta signaling.

This article has been cited by other articles:

				K. A. Pike, S. Iacampo, J. E. Friedmann, and M. J. H. Ratcliffe The Cytoplasmic Domain of Ig{alpha} Is Necessary and Sufficient to Support Efficient Early B Cell Development J. Immunol., February 15, 2004; 172(4): 2210 - 2218. [Abstract] [Full Text] [PDF]

				S. Tomita, H.-B. Jiang, T. Ueno, S. Takagi, K. Tohi, S.-i. Maekawa, A. Miyatake, A. Furukawa, F. J. Gonzalez, J. Takeda, et al. T Cell-Specific Disruption of Arylhydrocarbon Receptor Nuclear Translocator (Arnt) Gene Causes Resistance to 2,3,7,8-Tetrachlorodibenzo-p-dioxin-Induced Thymic Involution J. Immunol., October 15, 2003; 171(8): 4113 - 4120. [Abstract] [Full Text] [PDF]

				F. Vaillant, K. Blyth, L. Andrew, J. C. Neil, and E. R. Cameron Enforced Expression of Runx2 Perturbs T Cell Development at a Stage Coincident with {beta}-Selection J. Immunol., September 15, 2002; 169(6): 2866 - 2874. [Abstract] [Full Text] [PDF]

				A.-M. Steff, S. Trop, M. Maira, J. Drouin, and P. Hugo Opposite Ability of Pre-TCR and {{alpha}}{{beta}}TCR to Induce Apoptosis J. Immunol., April 15, 2001; 166(8): 5044 - 5050. [Abstract] [Full Text] [PDF]

				M. A. Berger, M. Carleton, M. Rhodes, J. M. Sauder, S. Trop, R. L. Dunbrack, P. Hugo, and D. L. Wiest Identification of a novel pre-TCR isoform in which the accessibility of the TCR{beta} subunit is determined by occupancy of the `missing' V domain of pre-T{alpha} Int. Immunol., November 1, 2000; 12(11): 1579 - 1591. [Abstract] [Full Text] [PDF]

				M. Kaneta, M. Osawa, M. Osawa, K. Sudo, H. Nakauchi, A. G. Farr, and Y. Takahama2 A Role for Pref-1 and HES-1 in Thymocyte Development J. Immunol., January 1, 2000; 164(1): 256 - 264. [Abstract] [Full Text] [PDF]

				M. Carleton, N. R. Ruetsch, M. A. Berger, M. Rhodes, S. Kaptik, and D. L. Wiest Signals Transduced by CD3{epsilon}, But Not by Surface Pre-TCR Complexes, Are Able to Induce Maturation of an Early Thymic Lymphoma In Vitro J. Immunol., September 1, 1999; 163(5): 2576 - 2585. [Abstract] [Full Text] [PDF]

				D. Shukla, C. L. Rowe, Y. Dong, V. R. Racaniello, and P. G. Spear The Murine Homolog (Mph) of Human Herpesvirus Entry Protein B (HveB) Mediates Entry of Pseudorabies Virus but Not Herpes Simplex Virus Types 1 and 2 J. Virol., May 1, 1999; 73(5): 4493 - 4497. [Abstract] [Full Text]

				M. S. Vacchio and J. D. Ashwell Thymus-derived Glucocorticoids Regulate Antigen-specific Positive Selection J. Exp. Med., June 2, 1997; 185(11): 2033 - 2038. [Abstract] [Full Text] [PDF]