Tetracycline-controllable selection of CD4(+) T cells: half-life and survival signals in the absence of major histocompatibility complex class II molecules.
A system that allows the study, in a gentle fashion, of the role of MHC molecules in naive T cell survival is described. Major histocompatibility complex class II-deficient mice were engineered to express Ealpha chains only in thymic epithelial cells in a tetracycline (tet)-controllable manner. This resulted in tet-responsive display of cell surface E complexes, positive selection of CD4(+)8(-) thymocytes, and generation of a CD4(+) T cell compartment in a class II-barren periphery. Using this system, we have addressed two unresolved issues: the half-life of naive CD4(+) T cells in the absence of class II molecules (3-4 wk) and the early signaling events associated with class II molecule engagement by naive CD4(+) T cells (partial CD3 zeta chain phosphorylation and ZAP-70 association).
Witherden
D
D
Institut de G¿en¿etique et de Biologie Mol¿eculaire et Cellulaire (CNRS/INSERM/ULP), 67404 Illkirch cedex, Strasbourg, France.
van Oers
N
N
Waltzinger
C
C
Weiss
A
A
Benoist
C
C
Mathis
D
D
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000187:drug effects; D002352:Carrier Proteins; D002454:Cell Differentiation; D002470:Cell Survival; D005786:Gene Expression Regulation; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D013752:Tetracycline / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D002352:Carrier Proteins; D000949:Histocompatibility Antigens Class II; D012097:Repressor Proteins; C083139:Tet O resistance protein, Bacteria; C034811:tetracycline resistance-encoding transposon repressor protein; D013752:Tetracycline