The selective expansion of functional T cell subsets.
Adoptive cellular immunotherapy is considered a potential treatment for a wide range of diseases, including cancer, infectious diseases, and autoimmune disorders. We have developed a method using a conditioned medium, XLCM, that selectively expands several different T cell subsets with a view to their use in cell therapy. Primary FBS-free suspension cultures of human peripheral blood low-density mononuclear cells treated with XLCM reproducibly expand over 100,000-fold within a period of 4 weeks. CD4+ T cells and CD8+ T cells expand sequentially in the unfractionated cultures, and relatively pure populations of CD4+ and CD8+ T cells may be expanded from populations first enriched in the respective T cell subset. CD4+ T cells cultured in XLCM produce cytokines consistent with the expansion of Th1, Th2, and Th0 subsets, whereas CD8+ T cells cultured in XLCM are cytolytically competent. An interesting feature of T cells cultured in XLCM is the persistence of 5%-10% CD4+CD8+ double-positive T cells in spite of substantial single-positive T cell expansion, suggesting that these cells also proliferate in XLCM. In addition to subsets of TCRalphabeta+ T cells, TCRgammadelta+ T cells are also significantly expanded by XLCM. These results demonstrate that XLCM efficiently expands several functional T cell subsets and provides a means of obtaining selected populations suitable for use in cellular immunotherapy.
Skea
D
D
Hemosol Incorporated, Etobicoke, Ontario, Canada.
Hedge
R
R
Dabek
B
B
Wettlaufer
B
B
Wong
T
T
Bell
D
D
D019264:Adoptive Transfer; D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology*; D018929:Cell Culture Techniques / Q000379:methods; D002455:Cell Division; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D016207:Cytokines / Q000096:biosynthesis; D006801:Humans; D016130:Immunophenotyping; D008213:Lymphocyte Activation; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology
D017077:Culture Media, Conditioned; D016207:Cytokines; D016692:Receptors, Antigen, T-Cell, gamma-delta