title: Preferential migration of T regulatory cells induced by IL-16.
abstract: As a natural ligand for CD4, IL-16 has been shown to preferentially induce migration in Th1 cells, and, in long-term cultures with IL-2, IL-16 facilitates the expansion of CD4(+)CD25(+) cells. In addition, IL-16 has an immunomodulatory role in asthmatic inflammation, as exogenous administration significantly reduces inflammation and airway hyperreactivity. The mechanism for this, however, is not clear. Based on its functional characteristics and potential immunomodulatory role, we investigated the ability of IL-16 to recruit and influence the development of T regulatory (Treg) cells. We now demonstrate that IL-16 preferentially induces migration in a CD25(+)CTLA-4(+) human T cell subset and that responding cells produce IFNgamma and TGFbeta but not IL-10. These cells are relatively unresponsive to antigenic stimulation and can suppress proliferation and IL-5, but not IFNgamma, production by autologous T cells. We further demonstrate that IL-16-recruited cells are enriched for Forkhead box P3 (Foxp3). In addition, we find that IL-16 stimulation may facilitate de novo induction of Foxp3(+) Treg cells, because the stimulation of FoxP3-negative T cells for 48 h results in the expression of FoxP3 mRNA and protein. These data indicate that at sites of inflammation IL-16 may contribute to selective Treg cell expansion through the preferential induction of a migratory response from existing Treg cells, as well as by the induction of de novo generation of FoxP3(+) cells. These findings offer a potential mechanism for the immunosuppressive effects of IL-16 seen in Th2-mediated inflammation.
authors.affiliation: The Pulmonary Center, Boston University School of Medicine, Boston, MA 02118, USA.
authors.forename: Caroline
authors.initials: C
authors.lastname: McFadden
authors.forename: Ross
authors.initials: R
authors.lastname: Morgan
authors.forename: Shilpa
authors.initials: S
authors.lastname: Rahangdale
authors.forename: Daniel
authors.initials: D
authors.lastname: Green
authors.forename: Hisato
authors.initials: H
authors.lastname: Yamasaki
authors.forename: David
authors.initials: D
authors.lastname: Center
authors.forename: William
authors.initials: W
authors.lastname: Cruikshank
mesh_terms: D015703:Antigens, CD / Q000276:immunology; D000943:Antigens, Differentiation / Q000276:immunology; D001249:Asthma / Q000276:immunology*; D060908:CTLA-4 Antigen; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology / Q000494:pharmacology; D051858:Forkhead Transcription Factors; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects; D007249:Inflammation / Q000276:immunology; D019410:Interleukin-16 / Q000276:immunology* / Q000494:pharmacology; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D050378:T-Lymphocytes, Regulatory; D018417:Th1 Cells; D018418:Th2 Cells / Q000276:immunology; D013997:Time Factors
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D016207:Cytokines; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D019410:Interleukin-16; D053645:Interleukin-2 Receptor alpha Subunit