Establishment of a karyotypically normal cytotoxic leukemic T-cell line from a T-ALL sample engrafted in SCID mice.
Bone marrow (BM) cells from a child with an immature (CD3-) acute T lymphoblastic leukemia (T-ALL) bearing no chromosomal abnormalities failed to grow in long-term culture in the presence or absence of recombinant human (rh) growth factors but could be engrafted in severe combined immunodeficient (SCID) mice and induced leukemia. The leukemic cells recovered from the animal tissues could be adapted to grow in vitro in the presence of rh interleukin-2 (IL-2) and give rise to a growth factor-dependent cell line designated TALL-107. This cell line expresses T-cell-specific mature markers (CD2, CD3/T-cell receptor [TCR] alpha beta, CD8, CD56), and its growth can be inhibited by IL-4 of all the cytokines tested. Similar to the original leukemic blasts, TALL-107 cells are clonal, have rearranged TCR-beta, gamma, and delta loci, and a normal 46 XY karyotype. However, unlike the patient's BM cells, the TALL-107 cell line displays potent tumoricidal activity that is not major histocompatibility complex restricted. The magnitude of mRNA expression of perforin and serine esterases and of lytic activity depends on the doses of IL-2 added. TALL-107 cells can also be triggered by CD3- and CD2-specific monoclonal antibodies (MoAbs) to mediate reverse tumor cell lysis. In addition, this cell line produces high levels of interferon gamma and tumor necrosis factor alpha on stimulation with anti-CD3 and/or anti-CD2 MoAb both in the presence or absence of IL-2. The overall data indicate that the SCID mouse is able to support the functional maturation and expansion of a cytotoxic T-cell subset from some types of T-ALL.
Cesano
A
A
Wistar Institute of Anatomy and Biology, Philadelphia, PA 19104.
O'Connor
R
R
Nowell
P C
PC
Lange
B
B
Clark
S C
SC
Santoli
D
D
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000032:analysis; D015139:Blotting, Southern; D001853:Bone Marrow / Q000276:immunology / Q000473:pathology; D002648:Child; D046508:Culture Techniques / Q000379:methods; D015329:Gene Rearrangement, T-Lymphocyte; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D007621:Karyotyping; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D013936:Thymidine / Q000378:metabolism; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D007376:Interleukin-2; D012333:RNA, Messenger; D011994:Recombinant Proteins; D015847:Interleukin-4; D013936:Thymidine