IL-7/STAT5 cytokine signaling pathway is essential but insufficient for maintenance of naive CD4 T cell survival in peripheral lymphoid organs.
Constitutive expression of suppressors of cytokine signaling (SOCS)1 in T lineage in vivo attenuated cytokine signaling and resulted in a dramatic reduction in the number of naive CD44(low)CD62L(high) CD4 T cells in the spleen. After adoptive transfer of thymocytes from SOCS1 transgenic mice into normal recipients, naive CD4 T cells rapidly disappeared from the spleen within 1 wk. Likewise, T cell-specific deletion of STAT5a/b in vivo resulted in a similar phenotype characterized by loss of naive CD4 T cells. Thus, STAT5-mediated signaling is crucial for promoting naive T cell survival. However, forced expression of constitutively active STAT5 failed to rescue CD4 T cells in SOCS1 transgenic mice, implying that STAT5 activation is necessary but not sufficient for naive CD4 T cell survival. Although blockade of the IL-7R, a SOCS1 target, resulted in clear inhibition of naive T cell survival, the effect occurred 3 wk after anti-IL-7R Ab treatment, but not at earlier time points. These results suggest that IL-7-mediated STAT5 activation is essential for long-term survival of naive CD4 cells after export from thymus, and that another SOCS1-sensitive cytokine is critical for short-term naive T cell survival.
Seki
Yoh-Ichi
Y
Laboratory for Signal Network, Research Center for Allergy and Immunology, RIKEN Yokohama Institute, Kanagawa, Japan.
Yang
Jianying
J
Okamoto
Mariko
M
Tanaka
Shinya
S
Goitsuka
Ryo
R
Farrar
Michael A
MA
Kubo
Masato
M
D019264:Adoptive Transfer; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D018106:CD28 Antigens / Q000032:analysis / Q000235:genetics; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000637:transplantation; D002470:Cell Survival; D016207:Cytokines / Q000378:metabolism; D007156:Immunologic Memory; D015851:Interleukin-7 / Q000378:metabolism*; D008221:Lymphoid Tissue / Q000166:cytology / Q000276:immunology; D051379:Mice; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D020395:Receptors, Interleukin-7 / Q000037:antagonists & inhibitors; D050799:STAT5 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013154:Spleen / Q000166:cytology / Q000276:immunology; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000502:physiology*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology*
D000906:Antibodies; D018106:CD28 Antigens; D016207:Cytokines; D015851:Interleukin-7; D011948:Receptors, Antigen, T-Cell; D020395:Receptors, Interleukin-7; D050799:STAT5 Transcription Factor; C491590:Socs1 protein, mouse; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins