T-cell differentiation of human and non-human primate CD34+ hematopoietic progenitor cells using porcine thymic stroma.
Transplantation of swine thymic tissue has been proposed as an approach to reconstitute the immune system of HIV-infected individuals. This is an attractive strategy because miniature swine are readily available as donors and porcine tissue is resistant to infection with HIV-1. Demonstration that porcine thymus tissue supports primate T-cell differentiation is critical to the ultimate utility of this approach. Using a thymic stroma culture system we have previously described [Rosenzweig M, Marks DF, Zhu H et al. In vitro T lymphopoiesis of human and rhesus CD34+ progenitor cells. Blood 1996; 87: 4040], we demonstrate that porcine thymus tissue is able to promote the in vitro T-lymphocyte differentiation of both human and non-human primate hematopoietic progenitor cells. CD34+ hematopoietic progenitors differentiated into both double positive (CD4+CD8+) and single positive thymocytes expressing CD4 or CD8 alone. A polyclonal T-cell repertoire was evident. In addition, the T cells responded appropriately to mitogen and were permissive to infection with simian immunodeficiency virus (SIV). These data demonstrate the ability of porcine thymus to support T-cell differentiation of both human and non-human hematopoietic progenitor cells and support in vivo studies of transplantation of swine thymic tissue as a strategy for immune reconstitution in AIDS.
Rosenzweig
M
M
Division of Immunology, Harvard Medical School, New England Regional Primate Research Center, Southborough, MA, USA. michael_rosenzweig@hms.harvard.edu
Yamada
K
K
Harper
D M
DM
Hempel
D M
DM
Johnson
R P
RP
D000818:Animals; D018952:Antigens, CD34 / Q000032:analysis; D015415:Biomarkers / Q000032:analysis; D018929:Cell Culture Techniques / Q000379:methods; D002478:Cells, Cultured; D019674:Genes, T-Cell Receptor beta; D015658:HIV Infections / Q000276:immunology / Q000628:therapy; D015497:HIV-1; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000276:immunology; D006801:Humans; D019891:Leukopoiesis; D008213:Lymphocyte Activation; D017710:Lymphocyte Transfusion; D008253:Macaca mulatta; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology*; D015302:Simian Immunodeficiency Virus; D017154:Stromal Cells / Q000166:cytology; D013552:Swine; D013556:Swine, Miniature; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology; D014183:Transplantation, Heterologous / Q000276:immunology
D018952:Antigens, CD34; D015415:Biomarkers