title: STAT5 is critical to maintain effector CD8+ T cell responses.
abstract: During an immune response, most effector T cells die, whereas some are maintained and become memory T cells. Factors controlling the survival of effector CD4(+) and CD8(+) T cells remain unclear. In this study, we assessed the role of IL-7, IL-15, and their common signal transducer, STAT5, in maintaining effector CD4(+) and CD8(+) T cell responses. Following viral infection, IL-15 was required to maintain a subpopulation of effector CD8(+) T cells expressing high levels of killer cell lectin-like receptor subfamily G, member 1 (KLRG1), and lower levels of CD127, whereas IL-7 and IL-15 acted together to maintain KLRG1(low)CD127(high) CD8(+) effector T cells. In contrast, effector CD4(+) T cell numbers were not affected by the individual or combined loss of IL-15 and IL-7. Both IL-7 and IL-15 drove phosphorylation of STAT5 within effector CD4(+) and CD8(+) T cells. When STAT5 was deleted during the course of infection, both KLRG1(high)CD127(low) and KLRG1(low)CD127(high) CD8(+) T cells were lost, although effector CD4(+) T cell populations were maintained. Furthermore, STAT5 was required to maintain expression of Bcl-2 in effector CD8(+), but not CD4(+), T cells. Finally, IL-7 and IL-15 required STAT5 to induce Bcl-2 expression and to maintain effector CD8(+) T cells. Together, these data demonstrate that IL-7 and IL-15 signaling converge on STAT5 to maintain effector CD8(+) T cell responses.
authors.affiliation: Division of Immunobiology, Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
authors.forename: Pulak
authors.initials: P
authors.lastname: Tripathi
authors.forename: Sema
authors.initials: S
authors.lastname: Kurtulus
authors.forename: Sara
authors.initials: S
authors.lastname: Wojciechowski
authors.forename: Allyson
authors.initials: A
authors.lastname: Sholl
authors.forename: Kasper
authors.initials: K
authors.lastname: Hoebe
authors.forename: Suzanne C
authors.initials: SC
authors.lastname: Morris
authors.forename: Fred D
authors.initials: FD
authors.lastname: Finkelman
authors.forename: H Leighton
authors.initials: HL
authors.lastname: Grimes
authors.forename: David A
authors.initials: DA
authors.lastname: Hildeman
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D005434:Flow Cytometry; D019409:Interleukin-15 / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D053646:Interleukin-2 Receptor beta Subunit / Q000276:immunology / Q000378:metabolism; D015851:Interleukin-7 / Q000276:immunology / Q000494:pharmacology; D053699:Interleukin-7 Receptor alpha Subunit / Q000276:immunology / Q000378:metabolism; D008216:Lymphocytic Choriomeningitis / Q000276:immunology* / Q000821:virology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050799:STAT5 Transcription Factor / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology
chemical_list: D019409:Interleukin-15; D053646:Interleukin-2 Receptor beta Subunit; D015851:Interleukin-7; D053699:Interleukin-7 Receptor alpha Subunit; D019253:Proto-Oncogene Proteins c-bcl-2; D050799:STAT5 Transcription Factor