Synergistic and antagonistic effects of IL-1 alpha and IL-4, respectively, on the IL-2-dependent growth of a T cell receptor-gamma delta+ human T leukemia cell line.
The TALL-103/2 cell line was derived from an immature acute T lymphocytic leukemia with T-myeloid differentiating capacity. The leukemic cells were first expanded in recombinant human IL-3 in which they acquired a myeloid phenotype, and subsequently were adapted to grow in human rIL-2 in which they became lymphoid committed. The TALL-103/2 cell line expresses only T cell-specific differentiation Ag (CD2, CD3, CD7, and CD8) but has retained the CD33 myeloid Ag originally present on the IL-3 expanded population. By using mAb directed at the TCR-alpha beta or specific for framework determinants on human TCR-gamma and -delta chains, the TALL-103/2 cells were shown to be WT31-, TCR delta 1+, TCS-1+, and Ti gamma A-, thus representing a T cell subset expressing the nondisulfide-linked form of the TCR-gamma delta. The TALL-103/2 cells have been maintained for more than 1 y in the presence of human rIL-2 on which they are strictly dependent. Chemical cross-linking and immunofluorescence studies indicate the presence of both high and intermediate affinity IL-2R on the TALL-103/2 cells. Whereas mAb antiTac and H-31 with reactivity to the IL-2R alpha-chain (p55) compete only partially for the IL-2-induced proliferation of these cells, mAb TU27, specific to the IL-2R beta-subunit (p75), inhibits such growth completely even at high concentrations of IL-2. The interactions of the two T cell-stimulating factors IL-1 and IL-4 on the IL-2-dependent growth of TALL-103/2 cells were investigated. IL-1 alpha synergizes with IL-2 in supporting the short and long term growth of this cell line, whereas IL-4 abrogates its growth. These effects are, at least in part, due to the modulation of IL-2R expression induced by the two lymphokines. Functionally, the TALL-103/2 cells display MHC-nonrestricted cytotoxic activity that is significantly enhanced by addition of either IL-4, IL-6, or IFN-gamma. Because of its properties and its stable requirement for IL-2 for continuous growth, this T lymphocytic leukemia-derived cell line represents an interesting model to analyze ontogeny and function of leukemic T cells.
Santoli
D
D
Wistar Institute of Anatomy and Biology, Philadelphia, PA 19104.
O'Connor
R
R
Cesano
A
A
Phillips
P
P
Colt
T L
TL
Lange
B
B
Clark
S C
SC
Rovera
G
G
D015703:Antigens, CD / Q000032:analysis; D002455:Cell Division / Q000187:drug effects; D003602:Cytotoxicity, Immunologic; D004357:Drug Synergism; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D007375:Interleukin-1 / Q000494:pharmacology*; D007376:Interleukin-2 / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology*; D008285:Major Histocompatibility Complex; D011948:Receptors, Antigen, T-Cell / Q000145:classification*; D015375:Receptors, Interleukin-2 / Q000502:physiology; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology* / Q000276:immunology; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D007375:Interleukin-1; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2; D015847:Interleukin-4