Disruption of T cell homeostasis in mice expressing a T cell-specific dominant negative transforming growth factor beta II receptor.
The immune system, despite its complexity, is maintained at a relative steady state. Mechanisms involved in maintaining lymphocyte homeostasis are poorly understood; however, recent availability of transgenic (Tg) and knockout mouse models with altered balance of lymphocyte cell populations suggest that cytokines play a major role in maintaining lymphocyte homeostasis. We show here that transforming growth factor (TGF)-beta plays a critical role in maintaining CD8(+) T cell homeostasis in a Tg mouse model that specifically overexpresses a dominant negative TGF-beta II receptor (DNRII) on T cells. DNRII T cell Tg mice develop a CD8(+) T cell lymphoproliferative disorder resulting in the massive expansion of the lymphoid organs. These CD8(+) T cells are phenotypically "naive" except for the upregulation of the cell surface molecule CD44, a molecule usually associated with memory T cells. Despite their dominance in the peripheral lymphoid organs, CD8(+) T cells appear to develop normally in the thymus, suggesting that TGF-beta exerts its homeostatic control in the peripheral immune system.
Lucas
P J
PJ
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Kim
S J
SJ
Melby
S J
SJ
Gress
R E
RE
D000818:Animals; D015703:Antigens, CD / Q000032:analysis / Q000145:classification; D001665:Binding Sites; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002453:Cell Cycle; D002460:Cell Line; D006706:Homeostasis; D006801:Humans; D016130:Immunophenotyping; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology; D013997:Time Factors
D015703:Antigens, CD; D018125:Receptors, Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II