title: Expansion of melanoma-specific lymphocytes in alternate gamma chain cytokines: gene expression variances between T cells and T-cell subsets exposed to IL-2 versus IL-7/15.
abstract: We have previously demonstrated that expansion of activated tumor-sensitized T cells in interleukin (IL)-7/15 results in greater expansion and antitumor activity than expansion in IL-2. We sought to determine whether T cells exposed to IL-2 versus IL-7/15 exhibited distinct gene expression patterns. Lymphocytes were harvested from Pmel-1 mice immunized with B16-GMCSF melanoma cells, activated in vitro, and cultured in IL-2 or IL-7/15 for 1, 3 or 6 days. T cells were harvested and analyzed using microarray, real-time quantitative polymerase chain reaction (RT-QPCR) or sorted into T-cell subsets and analyzed. We found significant differences in gene expression for T cells cultured in IL-2 versus IL-7/15, starting on day 3. This was not a function of subset differentiation; when T cells were divided into subsets, the central memory (T(CM)), effector memory (T(EM)) and effector (T(E)) T cells cultured in the IL-2 more closely resembled each other than the identical phenotypic subset exposed to IL-7/15. Thus, the differences in gene expression induced by culture in IL-2 versus IL-7/15 do not merely reflect differences in the frequency of T(CM) versus T(EM) versus T(E) cells, but rather reflect that the gene expression levels of those T-cell subsets when exposed to different cytokines are fundamentally different.
authors.affiliation: Department of Surgery, Virginia Commonwealth University Health System, Richmond, VA, USA.
authors.forename: C K
authors.initials: CK
authors.lastname: Zoon
authors.affiliation: Division of Surgical Oncology, Massey Cancer Center, Virginia Commonwealth University, Richmond, VA, USA.
authors.forename: E
authors.initials: E
authors.lastname: Seitelman
authors.affiliation: Department of Microbiology and Immunology, Massey Cancer Center, Virginia Commonwealth University, Richmond, VA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Keller
authors.affiliation: Division of Surgical Oncology, Massey Cancer Center, Virginia Commonwealth University, Richmond, VA, USA.
authors.forename: L
authors.initials: L
authors.lastname: Graham
authors.affiliation: Department of Pathology, Virginia Commonwealth University Health System, Richmond, VA, USA.
authors.forename: T L
authors.initials: TL
authors.lastname: Blevins
authors.affiliation: Department of Pathology, Virginia Commonwealth University Health System, Richmond, VA, USA.
authors.forename: C I
authors.initials: CI
authors.lastname: Dumur
authors.affiliation: 1] Department of Surgery, Virginia Commonwealth University Health System, Richmond, VA, USA [2] Division of Surgical Oncology, Massey Cancer Center, Virginia Commonwealth University, Richmond, VA, USA.
authors.forename: H D
authors.initials: HD
authors.lastname: Bear
mesh_terms: D000818:Animals; D016000:Cluster Analysis; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D016219:Immunotherapy, Adoptive; D019409:Interleukin-15 / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D015851:Interleukin-7 / Q000494:pharmacology; D008545:Melanoma / Q000235:genetics / Q000276:immunology* / Q000378:metabolism* / Q000628:therapy; D008546:Melanoma, Experimental; D051379:Mice; D008822:Mice, Transgenic; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*
chemical_list: D016207:Cytokines; D019409:Interleukin-15; D007376:Interleukin-2; D015851:Interleukin-7