A block in both early T lymphocyte and natural killer cell development in transgenic mice with high-copy numbers of the human CD3E gene.
A severe immunodeficiency involving a complete loss of T lymphocytes and natural killer cells was observed in independent lines of transgenic mice containing > 30 copies of the human CD3E gene (pL12). T-cell- natural killer (NK)- mice could also be generated by using a gene fragment pL12 delta 1 (without exons 4A and 5) coding for the CD3-epsilon transmembrane region and its 55-amino acid nonenzymatic cytoplasmic tail. The abnormally small thymus gland in the homozygous transgenic animals, which was approximately 1% the size of a wild-type thymus, contained only a few (2-4%) prethymocytes with a Thy-1+Pgp-1+IL-2R alpha- CD3-4-8- phenotype. In mice with lower copy numbers of the transgene thymocyte development was blocked at the Thy-1+Pgp-1-IL-2R alpha+CD3-4-8- stage, and normal NK activity was detected. Mice generated with high-copy numbers of a transgene pL12 delta 2 (pL12 delta 1 minus exons 6), coding for a truncated protein from which the CD3-epsilon extracellular domain, its transmembrane region, and most of its cytoplasmic region were absent, contained normal numbers of T lymphocytes and NK cells. These transgene effects suggested that recruitment of signal-transduction molecules by the cytoplasmic tail of this protein played an important role in the abrogation of both lineages. Taken together these observations support the notion that T lymphocytes and NK cells stemmed from a common precursor.
Wang
B
B
Division of Immunology, Beth Israel Hospital, Harvard Medical School, Boston, MA 02215.
Biron
C
C
She
J
J
Higgins
K
K
Sunshine
M J
MJ
Lacy
E
E
Lonberg
N
N
Terhorst
C
C
D000818:Animals; D000920:Antibody-Dependent Cell Cytotoxicity; D015703:Antigens, CD / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D017252:CD3 Complex / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D005091:Exons; D005434:Flow Cytometry; D006801:Humans; D015151:Immunoblotting; D016130:Immunophenotyping; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D015398:Signal Transduction; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D015703:Antigens, CD; D017252:CD3 Complex