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- Title
Mechanisms underlying T-lymphocyte activation: mitogen initiates and IL-2 amplifies the expression of transferrin receptors via intracellular iron level.
- Authors
Pelosi-Testa, E.; Samoggia, P.; Giannella, G.; Montesoro, E.; Caravita, T.; Salvo, G.; Camagna, A.; Isacchi, G.; Testa, U.; Peschle, C.
- Abstract
Peripheral blood mononuclear cells (PBM) pulsed with lectin (PHA or Con A for 0.25-3 hr) show a low expression of interleukin-2 and transferrin receptors (IL-2Rs, TfRs) and a mild decline of intracellular ferritin level, compared to control cultures grown in continuous presence of mitogen. Interestingly, lectin-pulsed PBM do not release detectable amounts of IL-2 in the medium. Furthermore, expression of TfRs in these lymphocytes is not inhibited by addition of excess anti- IL-2 neutralizing monoclonal antibody, but is significantly inhibited by treatment with iron salts. These observations suggest that mitogen triggers an IL-2-independent expression of TfRs, at least in part via a decrease of intracellular iron level. Addition of either recombinant IL-2 (rILs2) or an iron chelator (picolinic acid) to lectin-pulsed PBM induces both a marked enhancement of TfR synthesis and a sharp decline of intracellular ferritin level, which are comparable to the corresponding pattern observed in control cultures. Conversely, addition of iron salts fully inhibits the increase of Tilt expression induced by rIL-2. These observations strongly suggest that the enhanced TfR synthesis elicited by rIL-2 is mediated by depletion of a regulatory intracellular iron pool. In line with these studies, >99% purified T lymphocytes stimulated by lectin show a low expression of TfPs, which is markedly enhanced by addition of exogenous rIL-2. Altogether, we postulate that: (i) in resting T lymphocytes the gene encoding TfR is apparently in a 'closed' configuration; (ii) even in the absence of IL-2 activity, a mitogen pulse is sufficient to initiate the expression of TfRs, at lent in part via a decline of intracellular iron level; and (iii) TfR synthesis is then largely amplified by IL-2, again via a decrease of the size of a regulatory intracellular iron pool.
- Subjects
INTERLEUKIN-2; INTERLEUKINS; T cells; TRANSFERRIN; BLOOD proteins; MONOCLONAL antibodies
- Publication
Immunology, 1988, Vol 64, Issue 2, p273
- ISSN
0019-2805
- Publication type
Article