title: Interleukin-7 signalling is sufficient to phenotypically and functionally prime human CD4 naive T cells.
abstract: Interleukin-7 (IL-7) is produced by bone marrow and lymphoid stromal cells and is involved in the synthesis, survival and homeostasis of T cells. These attributes are the basis for current strategies to utilize IL-7 as an immune modulator for several clinical conditions to replenish depleted T-cell numbers. Because we had previously determined that IL-7 can induce potent human immunodeficiency virus replication in the otherwise non-permissive CD4(+) naive T-cell compartment, we evaluated here the impact of IL-7 on the phenotype and functional potential of naive CD4(+) T cells in an attempt to understand the mechanism of this induction. We demonstrate that IL-7 mediated the up-regulation of CD25, CD95 and human leucocyte antigen-DR, while it did not alter the expression of CD45RO, CD69, CD40, or CD154. Examination of the cytokine profile of IL-7-treated naive T cells using a Type1/Type2 Proteome Array indicated a remarkable IL-7-mediated induction of interferon-gamma production, while the other cytokines evaluated (IL-2, IL-12, tumour necrosis factor-alpha, IL-4, IL-5, IL-10 and IL-13) were not affected. Intracellular staining of IL-7-treated naive T cells for interferon-gamma verified the Proteome data. IL-7 did not induce cell cycle proliferation of naive CD4(+) T cells, as evaluated by 7-AAD/pyronin immunostaining and carboxyfluorescein diacetate succinimidyl ester dye tracking. IL-7 treatment of naive CD4(+) T cells induced their ability to prime monocytes, as was indicated by induction of CD80 and CD86 expression on monocytes cocultured with IL-7-treated naive CD4(+) T cells. Collectively, these data indicate that IL-7 signalling is sufficient to phenotypically and functionally prime human CD4(+) naive T cells independent of antigen stimulation.
authors.affiliation: Department of Immunology and Microbiology, Rush University Medical Center, Chicago, IL 60612, USA.
authors.forename: Elizabeth Z
authors.initials: EZ
authors.lastname: Managlia
authors.forename: Alan
authors.initials: A
authors.lastname: Landay
authors.forename: Lena
authors.initials: L
authors.lastname: Al-Harthi
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002453:Cell Cycle / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000096:biosynthesis; D006801:Humans; D016130:Immunophenotyping; D015851:Interleukin-7 / Q000276:immunology*; D017493:Leukocyte Common Antigens / Q000032:analysis; D015398:Signal Transduction / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*
chemical_list: D016207:Cytokines; D015851:Interleukin-7; D017493:Leukocyte Common Antigens
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