| Abstract |
Interleukin 2 is a growth factor that supports the proliferation and differentiation of T lymphocytes. Its action on B and NK lymphocytes as well as on monocytes has been documented in in vitro studies. However the in vivo action of Il2 on these cells is yet to be determined. The functional Il2R consists of three distinct subunits; Il2 Rα or CD25 or Tac, Il2Rβ or CD122 and γc (common) or CD132. Combinations of these three chains correspond to different forms of the receptor with altered affinity to the hormone. The aim of the study was to describe the structure and function of Il2R on the malignant cells of B CLL. The main objective was to determine the prerequisitions for the in vivo Il2-induced proliferation of B CLL malignant cells and furthermore the capacity of other growth factors or mitogens to induce B CLL proliferation through the Il2- Il2R pathway. Results: In enriched B CLL population provided after cytotoxicity with anti-CD3 and anti-CD14, for which monoclonicity with JH Southern blot hybridization was established, we obtained the following: 1. The expression levels of a-chain Il2-R varies among cases. 2. Il2Ra mRNA contains only the 3,5 Kb fragment among the mature mRNA transcripts. 3. Il2Rb expression is low, as observed by immunofluorescence and Il2-I125 binding experiments. 4. The expression of high and low affinity receptors varies among patients. 5. Il4 and PMA increase Il2Ra expression. 6. Il4 and PMA increase to a lesser extent Il2Rb expression. 7. Il4 induces B CLL proliferation in 50% of cases. 8. Il4 induces B CLL proliferation only in cases where Il2 exerted proliferative effects. 9. Il4 acts either antagonistically,synergistically or does not influences at all the Il2 induced B CLL proliferation. Conclusion: Malignant B CLL cells could proliferate under the induction of Il2. They do not express the entire functional receptor of Il2,yet they do express unequally its chains, in several combinations among the different patients and stages of the disease. The sole presence of a single a-chain mRNA subtype, is indicative of stabilization in a cellular-induced stage, since the mature mRNA products of the a-chain gene can be expressed in several combinations during different time periods following stimulation of normal B-lymphocytes. Regarding the variable effect of rIl4 on Il2 function, it may be attributed to the common chain that the two hormones possess in their receptor molecules.
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Μοριακός και λειτουργικός χαρακτηρισμός του υποδοχέα της ιντερλευκίνης 2 στα νεοπλασματικά κύτταρα της χρόνιας λεμφογενούς λευχαιμίας
