title: In vitro expansion of human γδ and CD56(+) T-cells by Aspergillus-antigen loaded fast dendritic cells in the presence of exogenous interleukin-12.
abstract: Aspergillus fumigatus (Af) infection is especially prevalent after allogenic bone marrow transplantation (BMT) and causes invasive pulmonary aspergillosis. Human γδ T-cells have essential role in maintaining immune homeostasis and in the resistance of pathogens and tumors. Also, γδ T-cells may facilitate stem cells engraftment and decrease a life-threatening graft versus host disease after allogenic BMT. Moreover, expression of CD56 molecules on γδ T-cells increases their antitumor cytotoxic activity. This study reveals that Af-pulsed fast dendritic cells (fast-DCs, which generated within only 72 h) plus IL-12 and then IL-2 can propagate autologous γδ and CD56(+) T-cells in vitro and this expansion is sustained by repeating the stimulation (107.5 ± 13.9-fold and 37.6 ± 2.2-fold increase for γδ and CD56(+) T-cells, respectively, after three primings). Many of the expanded γδ and CD56(+) T-cells expressed CD8 molecules (29.6%-68.6%), while few of them expressed CD4 molecules (2.3%-17.5%). Also, ∼28% of the expanded γδ T-cells were CD56(+). On the other hand, the proliferation of γδ and CD56(+) T-cells significantly decreased (p < 0.001, <19-fold and 12-fold, respectively) in the absence of either Af-pulsed fast-DCs or IL-12 or in the presence of un-pulsed fast-DCs, indicating the importance of Af-antigens and IL-12 in inducing this expansion. The expansion of γδ and CD56(+) T-cells did not hamper the generation of Af-specific αβ T-cell effectors. The methodology described in this study, utilizing autologous Af-pulsed fast-DCs and IL-12, permits the rapid generation of Af-specific αβ T-cell effectors and propagation of γδ and CD56(+) T-cells in vitro.
authors.affiliation: Biological Science Department, College of Science, King Faisal University, Al-Hufof, Kingdom of Saudi Arabia. gamal_ramadan@hotmail.com
authors.forename: Gamal
authors.initials: G
authors.lastname: Ramadan
mesh_terms: D017951:Antigen Presentation / Q000276:immunology; D015703:Antigens, CD / Q000378:metabolism; D000946:Antigens, Fungal / Q000276:immunology*; D001232:Aspergillus fumigatus / Q000276:immunology*; D019002:CD56 Antigen / Q000378:metabolism*; D002478:Cells, Cultured; D003601:Cytotoxicity Tests, Immunologic; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D018664:Interleukin-12 / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D000946:Antigens, Fungal; D019002:CD56 Antigen; D007376:Interleukin-2; C522918:NCAM1 protein, human; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D018664:Interleukin-12