The interleukin (IL) 2 receptor beta chain is shared by IL-2 and a cytokine, provisionally designated IL-T, that stimulates T-cell proliferation and the induction of lymphokine-activated killer cells.
Late-phase human T-cell lymphotropic virus I-associated adult T-cell leukemia cells express IL-2 receptors (IL-2R) but no longer produce IL-2. We have reported that the IL-2-independent adult T-cell leukemia line HuT-102 secretes a cytokine, provisionally designated IL-T, that stimulates T-cell proliferation and lymphokine-activated killer cell activity. Stimulation of proliferation of the cytokine-dependent human T-cell line Kit-225 mediated by HuT-102-conditioned medium or by 3200-fold-purified IL-T was not blocked by the addition of antibodies against IL-2 or IL-2R alpha subunit. However, IL-T-mediated stimulation of this human T-cell line was inhibited by addition of Mik-beta 1, an antibody that binds specifically to IL-2R beta subunit. In addition, the activation of large granular lymphocytes to lymphokine-activated killer cells mediated by IL-T-containing conditioned medium was not blocked by antibodies directed toward IL-2 or IL-2 alpha but was inhibited by an antibody to IL-2R beta, suggesting the requirement of this receptor subunit for IL-T action. This conclusion was confirmed using an IL-3-dependent murine myeloid precursor cell line, 32D, that expresses IL-2R alpha and IL-2R gamma, but not IL-2R beta. Neither IL-2 nor IL-T stimulated 32D cell proliferation. However, after transfection with the gene encoding human IL-2R beta, 32D beta cells proliferated on addition of either cytokine. The IL-T-mediated stimulation of 32D beta proliferation was inhibited by an anti-IL-2R beta antibody but not by an anti-IL-2 antibody. Thus, the IL-T-mediated stimulation of T-cell and lymphokine-activated killer cell activation requires the expression of the IL-2R beta subunit.
Bamford
R N
RN
Metabolism Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Grant
A J
AJ
Burton
J D
JD
Peters
C
C
Kurys
G
G
Goldman
C K
CK
Brennan
J
J
Roessler
E
E
Waldmann
T A
TA
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007376:Interleukin-2 / Q000737:chemistry / Q000276:immunology*; D007377:Interleukin-3 / Q000276:immunology; D007378:Interleukins / Q000737:chemistry / Q000276:immunology*; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D015375:Receptors, Interleukin-2 / Q000737:chemistry / Q000276:immunology*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D007376:Interleukin-2; D007377:Interleukin-3; D007378:Interleukins; D015375:Receptors, Interleukin-2