T cell activation in the absence of interleukin 2 (IL 2) results in the induction of high-affinity IL 2 receptor unable to transmit a proliferative signal.
Although interleukin 2 (IL 2) clearly up-regulates the expression of the p55 chain of the IL 2 receptor (IL 2R) little is known about its role in the induction of the high-affinity IL 2R. Resting T lymphocytes were induced to express IL 2R under experimental conditions in which IL 2 production was not induced or was prevented. Under these conditions high- and low-affinity IL 2R were easily demonstrated by Scatchard analysis. Northern blot analysis confirmed the accumulation of p55 specific mRNA and the absence of the IL 2 transcript. High-affinity IL 2R induced in the complete absence of IL 2 were unable to transmit a proliferative response unless exposed to extremely high concentrations of IL 2. The addition of picomolar amounts of recombinant IL 2 or the initiation of endogenous IL 2 production during the induction period restored the functionality of high-affinity IL 2R. Also, T cells induced to generate IL 2 displayed functional high-affinity IL 2R even in the presence of monoclonal antibodies blocking extracellular IL 2 and IL 2R. These results indicate that the presence of IL 2 during the early phase of T cell activation is an absolute requirement for the induction of fully operational high-affinity IL 2R and that low amounts of intracellular IL 2 are sufficient to confer functional properties to these receptors. The data also suggest that an intracellular as well as an extracellular high-affinity structure, expressed as a consequence of cell activation, is responsible for conferring competence to the high-affinity IL 2R involved in IL 2-dependent proliferation.
Proust
J J
JJ
Clinical Immunology Section, National Institute of Aging, NIH, Baltimore, MD 21224.
Shaper
N L
NL
Buchholz
M A
MA
Nordin
A A
AA
D000818:Animals; D000911:Antibodies, Monoclonal; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000378:metabolism / Q000502:physiology*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis* / Q000378:metabolism; D011994:Recombinant Proteins; D013601:T-Lymphocytes / Q000502:physiology*
D000911:Antibodies, Monoclonal; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins; D015240:Phorbol 12,13-Dibutyrate