A role for STAT5A/B in protection of peripheral T-lymphocytes from postactivation apoptosis: insights from gene expression profiling.
Activation of the transcription factors STAT5A and STAT5B by JAK1 and JAK3 tyrosine kinases is a key event in downstream signaling of gammac (common gamma chain)-family cytokine receptors in lymphoid cells. STAT5A/B-deficiency in mice causes, among other consequences, a reduced size and altered composition of the peripheral T-cell pool with predominance of an activated or memory-like population (CD4(+)/CD44(high)/CD62L(low)) and a proliferative deficiency following antigenic stimulation and subsequent IL-2 treatment. To further elucidate the critical function of STAT5A/B in homeostasis and activation of murine naïve peripheral T-lymphocytes, we have analyzed global gene expression of STAT5A/B-deficient versus wild-type splenic T-cells by profiling with high-density oligonucleotide arrays (Affymetrix). Comparison of (1) basal gene expression of untreated peripheral STAT5A/B-deficient and control T-cells and (2) immediate early gene induction upon in vitro stimulation of either population with IL-2 has revealed differential expression of a broad range of genes potentially contributing to the defects of STAT5A/B deficient T-cells. In the context of enhanced apoptotic rates of STAT5A/B(-/-)-T-cells in vivo and upon TCR-stimulation in culture our data suggest a role for STAT5 in post-activation survival beyond regulation of antiapoptotic Bcl-2 proteins and hence provide new insights into the nature of the late proliferative block in the T-cell compartment caused by STAT5-deficiency.
Gatzka
Martina
M
Howard Hughes Medical Institute, St. Jude Children's Research Hospital, Memphis, TN 38120, USA. gatzka.tina@uci.edu
Piekorz
Roland
R
Moriggl
Richard
R
Rawlings
Jason
J
Ihle
James N
JN
D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D015152:Blotting, Northern; D015153:Blotting, Western; D016000:Cluster Analysis; D004789:Enzyme Activation; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D007376:Interleukin-2 / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D050799:STAT5 Transcription Factor / Q000172:deficiency / Q000302:isolation & purification / Q000378:metabolism*; D013154:Spleen / Q000166:cytology / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism*; D015533:Transcriptional Activation
D007376:Interleukin-2; D050799:STAT5 Transcription Factor