title: Disparate roles for STAT5 in primary and secondary CTL responses.
abstract: IL-2 signals during the primary response to infection are essential in shaping CD8(+) T cell fate decisions. How CD8(+) T cells integrate IL-2 signals in the development of functional memory is not well understood. Because IL-2 induces potent activation of the STAT5 transcription factor, we tested the role of STAT5 in CD8(+) memory T cell differentiation and function using a model system in which STAT5 activity is inducibly abrogated upon CD8(+) T cell activation. We report that STAT5 activity is broadly important for the expansion and effector function of all effector CTL subsets. After pathogen clearance, STAT5 was required for the survival of effector phenotype memory CTLs during the contraction phase. However, despite its role in supporting full primary CD8(+) T cell expansion, and unlike IL-2, STAT5 activity is not required for the development of memory CD8(+) T cells capable of robust secondary expansion upon rechallenge. Our findings highlight differential requirements for survival signals between primary and secondary effector CTL, and demonstrate that IL-2-dependent programming of memory CD8(+) T cells capable of secondary expansion and secondary effector differentiation is largely STAT5 independent.
authors: Department of Pathology, University of Utah, Salt Lake City, UT 84112, USA.
authors: Diana M
authors: DM
authors: Mitchell
authors: Matthew A
authors: MA
authors: Williams
mesh_terms: D000818:Animals; D001117:Arenaviridae Infections / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D015870:Gene Expression; D007156:Immunologic Memory / Q000235:genetics; D007376:Interleukin-2 / Q000276:immunology / Q000378:metabolism; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D050799:STAT5 Transcription Factor / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*
chemical_list: D007376:Interleukin-2; D050799:STAT5 Transcription Factor