title: Lack of IL-7 and IL-15 signaling affects interferon-γ production by, more than survival of, small intestinal intraepithelial memory CD8+ T cells.
abstract: Survival of antigen-specific CD8(+)  T cells in peripheral lymphoid organs during viral infection is known to be dependent predominantly on IL-7 and IL-15. However, little is known about a possible influence of tissue environmental factors on this process. To address this question, we studied survival of memory antigen-specific CD8(+)  T cells in the small intestine. Here, we show that 2 months after vaccinia virus infection, B8R(20-27) /H2-K(b)  tetramer(+)  CD8(+)  T cells in the small intestinal intraepithelial (SI-IEL) layer are found in mice deficient in IL-15 expression. Moreover, SI-IEL and lamina propria lymphocytes do not express the receptor for IL-7 (IL-7Rα/CD127). In addition, after in vitro stimulation with B8R(20-27)  peptide, SI-IEL cells do not produce high amounts of IFN-γ neither at 5 days nor at 2 months postinfection (p.i.). Importantly, the lack of IL-15 was found to shape the functional activity of antigen-specific CD8(+)  T cells, by narrowing the CTL avidity repertoire. Taken together, these results reveal that survival factors, as well as the functional activity, of antigen-specific CD8(+)  T cells in the SI-IEL compartments may markedly differ from their counterparts in peripheral lymphoid tissues.
authors.affiliation: Molecular Immunogenetics and Vaccine Research Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Dmitry
authors.initials: D
authors.lastname: Isakov
authors.forename: Amiran
authors.initials: A
authors.lastname: Dzutsev
authors.forename: Jay A
authors.initials: JA
authors.lastname: Berzofsky
authors.forename: Igor M
authors.initials: IM
authors.lastname: Belyakov
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D005260:Female; D018928:Immunity, Mucosal / Q000276:immunology; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology*; D019409:Interleukin-15 / Q000276:immunology* / Q000378:metabolism; D015851:Interleukin-7 / Q000276:immunology* / Q000378:metabolism; D053699:Interleukin-7 Receptor alpha Subunit / Q000276:immunology / Q000378:metabolism; D007413:Intestinal Mucosa / Q000276:immunology* / Q000378:metabolism; D007421:Intestine, Small / Q000276:immunology* / Q000378:metabolism; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D020395:Receptors, Interleukin-7 / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*; D014615:Vaccinia / Q000276:immunology
chemical_list: D019409:Interleukin-15; D015851:Interleukin-7; D053699:Interleukin-7 Receptor alpha Subunit; D016693:Receptors, Antigen, T-Cell, alpha-beta; D020395:Receptors, Interleukin-7; C415350:interleukin-7 receptor, alpha chain; D007371:Interferon-gamma