J. Exp. Med., Volume 187, Number 11, June 1, 1998 1839-1848

The Role of the Thymus and Recent Thymic Migrants in the Maintenance of the Adult Peripheral Lymphocyte Pool

By S.P. Berzins,^* R.L. Boyd,^* and J.F.A.P. Miller

From the ^* Department of Pathology and Immunology, Monash Medical School, Prahran 3181, Victoria, Australia; and the  Walter and Eliza Hall Institute of Medical Research, Parkville 3052, Victoria, Australia

The thymus is essential for the initial seeding of T cells to the periphery, but its role in maintaining the adult T cell pool remains poorly defined. We investigated whether changes to the rate of T cell export could form part of the mechanism(s) controlling the homeostatic regulation of the size and composition of the peripheral T cell pool. Using neonatal thymi grafted under the kidney capsule, we found that irrespective of whether the pool was oversupplied (by thymic grafts) or undersupplied (due to neonatal thymectomy), the thymic export rate was constant from both the host and graft thymus, and the periphery remained constant in size. Recent thymic emigrants (RTE) were also tracked to determine the extent of their acceptance into the T cell pool of a normal mouse. As a population, RTE are phenotypically mature, but were distinct from resident T cells in the periphery, being released in a CD4/CD8 ratio approximately twice that of established peripheral T cells. This export ratio is similar to that of T cells in the mature thymic compartment, but soon after entry into the periphery, the ratio falls, indicating separate thymic and peripheral regulation of the CD4/CD8 ratio. RTE may also be preferentially incorporated into the periphery, causing displacement of resident T cells, thus maintaining the size of the peripheral pool. Although not vital for the maintenance of a functional T cell pool, the acceptance of RTE in a "full" peripheral pool would ensure that the T cell receptor repertoire is kept diverse and that the T cell population encompasses a broad range of naive as well as memory T cells.

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• Cunningham, C. P., Kimpton, W. G., Fernando, A., Cahill, R. N. P. (2001). Neonatal thymectomy identifies two major pools of sessile and recirculating peripheral T cells which appear to be under separate homeostatic control. Int Immunol 13: 1351-1359 [Abstract] [Full Text]  
• Gudmundsdottir, H., Turka, L. A. (2001). A Closer Look at Homeostatic Proliferation of CD4+ T Cells: Costimulatory Requirements and Role in Memory Formation. J. Immunol. 167: 3699-3707 [Abstract] [Full Text]  
• Almeida, A. R.M., Borghans, J. A.M., Freitas, A. A. (2001). T Cell Homeostasis: Thymus Regeneration and Peripheral T Cell Restoration in Mice with a Reduced Fraction of Competent Precursors. JEM 194: 591-600 [Abstract] [Full Text]  
• Hassan, J., Reen, D. J. (2001). Human Recent Thymic Emigrants-Identification, Expansion, And Survival Characteristics. J. Immunol. 167: 1970-1976 [Abstract] [Full Text]  
• Dardalhon, V., Jaleco, S., Kinet, S., Herpers, B., Steinberg, M., Ferrand, C., Froger, D., Leveau, C., Tiberghien, P., Charneau, P., Noraz, N., Taylor, N. (2001). IL-7 differentially regulates cell cycle progression and HIV-1-based vector infection in neonatal and adult CD4+ T cells. Proc. Natl. Acad. Sci. USA 10.1073/pnas.161272698v1 [Abstract] [Full Text]  
• Fry, T. J., Connick, E., Falloon, J., Lederman, M. M., Liewehr, D. J., Spritzler, J., Steinberg, S. M., Wood, L. V., Yarchoan, R., Zuckerman, J., Landay, A., Mackall, C. L. (2001). A potential role for interleukin-7 in T-cell homeostasis. Blood 97: 2983-2990 [Abstract] [Full Text]  
• Mackall, C. L., Fry, T. J., Bare, C., Morgan, P., Galbraith, A., Gress, R. E. (2001). IL-7 increases both thymic-dependent and thymic-independent T-cell regeneration after bone marrow transplantation. Blood 97: 1491-1497 [Abstract] [Full Text]  
• Hoffacker, V., Schultz, A., Tiesinga, J. J., Gold, R., Schalke, B., Nix, W., Kiefer, R., Muller-Hermelink, H. K., Marx, A. (2000). Thymomas alter the T-cell subset composition in the blood: a potential mechanism for thymoma-associated autoimmune disease. Blood 96: 3872-3879 [Abstract] [Full Text]  
• Ferreira, C., Barthlott, T., Garcia, S., Zamoyska, R., Stockinger, B. (2000). Differential Survival of Naive CD4 and CD8 T Cells. J. Immunol. 165: 3689-3694 [Abstract] [Full Text]  
• Boileau, C., Houde, M., Dulude, G., Clegg, C. H., Perreault, C. (2000). Regulation of Extrathymic T Cell Development and Turnover by Oncostatin M. J. Immunol. 164: 5713-5720 [Abstract] [Full Text]  
• Annacker, O., Burlen-Defranoux, O., Pimenta-Araujo, R., Cumano, A., Bandeira, A. (2000). Regulatory CD4 T Cells Control the Size of the Peripheral Activated/Memory CD4 T Cell Compartment. J. Immunol. 164: 3573-3580 [Abstract] [Full Text]  
• Klug, D. B., Crouch, E., Carter, C., Coghlan, L., Conti, C. J., Richie, E. R. (2000). Transgenic Expression of Cyclin D1 in Thymic Epithelial Precursors Promotes Epithelial and T Cell Development. J. Immunol. 164: 1881-1888 [Abstract] [Full Text]  
• Arstila, T. P., Casrouge, A., Baron, V., Even, J., Kanellopoulos, J., Kourilsky, P. (1999). A Direct Estimate of the Human T Cell Receptor Diversity. Science 286: 958-961 [Abstract] [Full Text]  
• Damoiseaux, J. G. M. C., Cautain, B., Bernard, I., Mas, M., van Breda Vriesman, P. J. C., Druet, P., Fournie, G., Saoudi, A. (1999). A Dominant Role for the Thymus and MHC Genes in Determining the Peripheral CD4/CD8 T Cell Ratio in the Rat. J. Immunol. 163: 2983-2989 [Abstract] [Full Text]  
• Berzins, S. P., Godfrey, D. I., Miller, J. F. A. P., Boyd, R. L. (1999). A central role for thymic emigrants in peripheral T cell homeostasis. Proc. Natl. Acad. Sci. USA 96: 9787-9791 [Abstract] [Full Text]  
• Brochu, S., Rioux-Masse, B., Roy, J., Roy, D.-C., Perreault, C. (1999). Massive Activation-Induced Cell Death of Alloreactive T Cells With Apoptosis of Bystander Postthymic T Cells Prevents Immune Reconstitution in Mice With Graft-Versus-Host Disease. Blood 94: 390-400 [Abstract] [Full Text]  
• Berzins, S. P., Davey, G. M., Randle-Barrett, E. S., Malin, M. A., Classon, B. J., Fraser, S., Boyd, R. L. (1999). Thymic Shared Antigen-2: A Novel Cell Surface Marker Associated with T Cell Differentiation and Activation. J. Immunol. 162: 5119-5126 [Abstract] [Full Text]  
• Dulude, G., Roy, D.-C., Perreault, C. (1999). The Effect of Graft-versus-Host Disease on T Cell Production and Homeostasis. JEM 189: 1329-1342 [Abstract] [Full Text]  
• McFarland, R. D., Douek, D. C., Koup, R. A., Picker, L. J. (2000). Identification of a human recent thymic emigrant phenotype. Proc. Natl. Acad. Sci. USA 97: 4215-4220 [Abstract] [Full Text]  
• Dardalhon, V., Jaleco, S., Kinet, S., Herpers, B., Steinberg, M., Ferrand, C., Froger, D., Leveau, C., Tiberghien, P., Charneau, P., Noraz, N., Taylor, N. (2001). IL-7 differentially regulates cell cycle progression and HIV-1-based vector infection in neonatal and adult CD4+ T cells. Proc. Natl. Acad. Sci. USA 98: 9277-9282 [Abstract] [Full Text]  

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