title: IL-15 preferentially enhances functional properties and antigen-specific responses of CD4+CD28(null) compared to CD4+CD28+ T cells.
abstract: One of the most prominent changes during T-cell aging in humans is the accumulation of CD28(null) T cells, mainly CD8+ and also CD4+ T cells. Enhancing the functional properties of these cells may be important as they provide an antigen-specific defense against chronic infections. Recent studies have shown that IL-15 does in fact play an appreciable role in CD4 memory T cells under physiological conditions. We found that treatment with IL-15 increased the frequency of elderly CD4+CD28(null) T cells by the preferential proliferation of these cells compared to CD4+CD28+ T cells. IL-15 induced an activated phenotype in CD4+CD28(null) T cells. Although the surface expression of IL-15R α-chain was not increased, the transcription factor STAT-5 was preferentially activated. IL-15 augmented the cytotoxic properties of CD4+CD28(null) T cells by increasing both the mRNA transcription and storage of granzyme B and perforin for the cytolytic effector functions. Moreover, pretreatment of CD4+CD28(null) T cells with IL-15 displayed a synergistic effect on the IFN-γ production in CMV-specific responses, which was not observed in CD4+CD28+ T cells. IL-15 could play a role enhancing the effector response of CD4+CD28(null) T cells against their specific chronic antigens.
authors.affiliation: Department of Immunology, Hospital Universitario Central de Asturias, C ⁄ Julián Clavería s ⁄ n,Oviedo, Spain.
authors.forename: Rebeca
authors.initials: R
authors.lastname: Alonso-Arias
authors.forename: Marco A
authors.initials: MA
authors.lastname: Moro-García
authors.forename: José R
authors.initials: JR
authors.lastname: Vidal-Castiñeira
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Solano-Jaurrieta
authors.forename: Francisco M
authors.initials: FM
authors.lastname: Suárez-García
authors.forename: Eliecer
authors.initials: E
authors.lastname: Coto
authors.forename: Carlos
authors.initials: C
authors.lastname: López-Larrea
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000914:Antibodies, Viral / Q000032:analysis; D015415:Biomarkers; D018106:CD28 Antigens / Q000032:analysis / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology*; D049109:Cell Proliferation; D003587:Cytomegalovirus / Q000276:immunology; D053804:Granzymes / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D019409:Interleukin-15 / Q000276:immunology / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D008213:Lymphocyte Activation; D054353:Perforin / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000276:immunology / Q000494:pharmacology; D050799:STAT5 Transcription Factor / Q000235:genetics / Q000378:metabolism
chemical_list: D000914:Antibodies, Viral; D015415:Biomarkers; D018106:CD28 Antigens; D019409:Interleukin-15; D012333:RNA, Messenger; D011994:Recombinant Proteins; D050799:STAT5 Transcription Factor; D054353:Perforin; D007371:Interferon-gamma; D053804:Granzymes