Generation of mature CD3+ and T cell receptor (TCR) + T cells from a leukemic analogue of the putative human stem cell by T cell conditioned medium containing IL-3, IL-2, and GM-CSF.
Malignant cells of a patient with acute leukemia expressed hematopoietic stem cell antigens such as CD34 and HLA-class II but lacked lineage specific differentiation markers. The leukemic blasts differentiated into mature T cells within 14 days in the presence of a T cell conditioned medium or with a mixture of highly purified interleukin-2 (IL-2) plus recombinant interleukin-3 (IL-3) and recombinant granulocyte/macrophage colony-stimulating factor (GM-CSF). Phenotypically, the maturing cells acquired the T cell-specific differentiation antigens CD2, CD3, and CD8, whereas immature differentiation antigens such as CD34 and Leu19 as well as HLA-class II and the IL-2 receptor CD25 were concomitantly down-regulated within 14 days of in vitro culture. This in vitro maturation involved two to three synchronized cell divisions. Beyond 10 days of culture the leukemic cells produced mRNA specific for the T cell receptor beta and alpha chain, but at no time transcription of T cell receptor gamma chain-specific message was detectable. To our knowledge, these data represent the first in vitro model demonstrating the differentiation of phenotypically mature T cells from immature leukemic cells induced by the combined activities of IL-2 plus IL-3 and GM-CSF.
D018941:Antigens, CD19; D000944:Antigens, Differentiation, B-Lymphocyte / Q000032:analysis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis*; D002460:Cell Line; D003115:Colony-Stimulating Factors / Q000494:pharmacology*; D003470:Culture Media; D005260:Female; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology*; D007377:Interleukin-3 / Q000494:pharmacology*; D008875:Middle Aged; D010641:Phenotype; D011948:Receptors, Antigen, T-Cell / Q000032:analysis* / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*
D018941:Antigens, CD19; D000944:Antigens, Differentiation, B-Lymphocyte; D000945:Antigens, Differentiation, T-Lymphocyte; D003115:Colony-Stimulating Factors; D003470:Culture Media; D007376:Interleukin-2; D007377:Interleukin-3; D011948:Receptors, Antigen, T-Cell; D011994:Recombinant Proteins