Disruption of T Cell Homeostasis in Mice Expressing a T Cell-specific Dominant Negative Transforming Growth Factor {beta} II Receptor

doi:10.1084/jem.191.7.1187

Published online 3 April 2000.

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© The Rockefeller University Press, 0022-1007/2000/4/1187/ $5.00
The Journal of Experimental Medicine, Volume 191, Number 7, April 3, 2000 1187-1196

Original Article

Disruption of T Cell Homeostasis in Mice Expressing a T Cell–specific Dominant Negative Transforming Growth Factor ß II Receptor

Philip J. Lucas^a, Seong-Jin Kim^b, Spencer J. Melby^a, and Ronald E. Gress^a
^a Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892
^b Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892

Correspondence to: Ronald E. Gress, National Institutes of Health, 10 Center Dr. 10/4B-36, Bethesda, MD 20892. Tel:301-496-6898 Fax:301-496-0887 E-mail:gressr{at}exchange.nih.gov.

The immune system, despite its complexity, is maintained ata relative steady state. Mechanisms involved in maintaininglymphocyte homeostasis are poorly understood; however, recentavailability of transgenic (Tg) and knockout mouse models withaltered balance of lymphocyte cell populations suggest thatcytokines play a major role in maintaining lymphocyte homeostasis.We show here that transforming growth factor (TGF)-ß playsa critical role in maintaining CD8⁺ T cell homeostasis in aTg mouse model that specifically overexpresses a dominant negativeTGF-ß II receptor (DNRII) on T cells. DNRII T cell Tgmice develop a CD8⁺ T cell lymphoproliferative disorder resultingin the massive expansion of the lymphoid organs. These CD8⁺T cells are phenotypically "naive" except for the upregulationof the cell surface molecule CD44, a molecule usually associatedwith memory T cells. Despite their dominance in the peripherallymphoid organs, CD8⁺ T cells appear to develop normally inthe thymus, suggesting that TGF-ß exerts its homeostaticcontrol in the peripheral immune system.

Key Words: lymphoproliferative disorder, T lymphocyte subsets, TCR repertoire,T cell transformation, thymocyte development

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