Abstract
Cytokines that use the common gamma chain gammac are critical for lymphoid development and function. Mutations of the IL-7 receptor, gammac, or its associated kinase, Jak3, are the major cause of human severe combined immunodeficiency. Although activated by IL-7, Stat5a/b (Stat, signal transducer and activator of transcription) have been thought to play limited roles in lymphoid development. However, we now show that mice completely deficient in Stat5a/b have severely impaired lymphoid development and differentiation. Absence of Stat5 also abrogates T cell receptor gamma rearrangement and survival of peripheral CD8(+) T cells. Thus, deficiency of Stat5 results in severe combined immunodeficiency, similar in many respects to deficiency of IL-7R, gammac, and Jak3.
Publication types
-
Research Support, N.I.H., Intramural
MeSH terms
-
Animals
-
B-Lymphocytes / immunology
-
CD8-Positive T-Lymphocytes / virology
-
Cell Differentiation
-
Cell Proliferation
-
Cell Transplantation
-
Cytokines / metabolism
-
Flow Cytometry
-
Hyaluronan Receptors / biosynthesis
-
Janus Kinase 3
-
Liver / embryology
-
Lymphocytes / cytology*
-
Mice
-
Mice, SCID
-
Mutation
-
Protein-Tyrosine Kinases / genetics
-
Protein-Tyrosine Kinases / metabolism
-
RNA / metabolism
-
Receptors, Antigen, T-Cell / metabolism
-
Receptors, Interleukin-7 / genetics
-
Reverse Transcriptase Polymerase Chain Reaction
-
STAT5 Transcription Factor / genetics
-
STAT5 Transcription Factor / physiology*
-
Spleen / embryology
-
T-Lymphocytes / immunology
-
T-Lymphocytes / metabolism
-
Time Factors
Substances
-
Cytokines
-
Hyaluronan Receptors
-
Receptors, Antigen, T-Cell
-
Receptors, Interleukin-7
-
STAT5 Transcription Factor
-
Stat5a protein, mouse
-
Stat5b protein, mouse
-
RNA
-
Protein-Tyrosine Kinases
-
JAK3 protein, human
-
Jak3 protein, mouse
-
Janus Kinase 3