Thymosin-alpha1 stimulates maturation of CD34+ stem cells into CD3+4+ cells in an in vitro thymic epithelia organ coculture model.
The effect of thymosin-alpha1 on thymopoiesis is largely unknown. Thymosin is found in the cortical and medullary thymic epithelia, as well as in nurse cells; thus, it is hypothesized that thymosin may affect both early and late stage of thymocyte maturation. In this study, the effect of thymosin-alpha1 on thymopoiesis was determined by coculturing in vitro CD34+ stem cells (SC) with allogeneic cultured thymic epithelia fragments (CTEF) for 1-4 weeks and analyzing T-cell maturation by flow cytometry. Thymosin-alpha1 significantly enhanced the cell number (e.g., proliferation) of mononuclear cells obtained at 2 and 4 weeks of the SC-CTEF cocultures (P < 0.01 and < 0.05, respectively). In particular, thymosin-alpha1 stimulated expression of CD3+ cells at 3 and 4 weeks (P < 0.05). The predominant subpopulation increased by thymosin stimulation was single positive mature CD4+ cells, which was confirmed to occur within the SC-CTEF thymic organ tissue by laser confocal immunofluorescence microscopy. Thymosin stimulation tended to enhance IL-7 synthesis, critical cytokine in the maturation of thymocytes. In summary, this is the first study to demonstrate that thymosin-alpha1 enhanced thymopoiesis of CD34+ stem cells in humans using an in vitro model of differentiation using stem cells and cultured thymic epithelial fragments cocultures. Furthermore, the thymosin significantly increased expression of CD3+4+ T cells.
Pediatric Research Institute and Department of Pathology, St Louis University Health Sciences Center, Missouri 63110, USA. knutsenm.slu.edu.
A P
AP
Knutsen
J J
JJ
Freeman
K R
KR
Mueller
S T
ST
Roodman
J D
JD
Bouhasin
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D018952:Antigens, CD34 / Q000276:immunology*; D017252:CD3 Complex / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D002455:Cell Division / Q000187:drug effects; D018920:Coculture Techniques; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007223:Infant; D015851:Interleukin-7 / Q000096:biosynthesis; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D010641:Phenotype; D013234:Stem Cells / Q000187:drug effects* / Q000276:immunology; D013268:Stimulation, Chemical; D000077596:Thymalfasin; D013947:Thymosin / Q000031:analogs & derivatives* / Q000494:pharmacology; D013950:Thymus Gland / Q000166:cytology* / Q000254:growth & development / Q000276:immunology
D000276:Adjuvants, Immunologic; D018952:Antigens, CD34; D017252:CD3 Complex; D015851:Interleukin-7; D013947:Thymosin; D000077596:Thymalfasin