Independent expression of p55 and p75 interleukin‐2 receptors (IL‐2R) during intravenous or subcutaneous administration of recombinant interleukin‐2 (rIL‐2) by T‐lymphocytes and natural killer cells

Renato Zambello, Livio Trentin, Andrea Cerutti, Christine Enthammer, Antonella Milani, Tiziano Franceschi, Chiara Messina, Gian Luigi Cetto, Carlo Agostini, Gianpietro Semenzato

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Background. The effects of immunotherapy with re combinant interleukin‐2 (rIL‐2) on peripheral blood lymphocytes have been a matter of debate. In this study the authors addressed the issue of the biologic effects of two different schedules of rIL‐2 administration (i. e., continuous intravenous infusion versus subcutaneous injection) on the expression of the p55 and p75 chains of interleukin‐2 receptor (IL‐2R). Methods. Sixteen patients were studied: 6 patients with a previous diagnosis of acute leukemia entered the study at least +60 days (+63‐+144 days) after autologous bone marrow transplantation and were treated with continuous rIL‐2 infusion; 10 patients with advanced metastatic renal cancer were treated with subcutaneous rIL‐2 therapy. In both groups of patients, therapy consisted of two cycles of 5‐day rIL‐2, and immunologic evaluation was performed two days after completion of the second cycle. Results. Intravenous treatment was associated with a marked increase in CD56+ natural killer (NK) cells expressing the p75 but lacking the p55 IL‐2R; however, the absolute number of CD3+ lymphocytes was unchanged, and they showed a low or absent expression of the p55 and negativity for the p75 IL‐2R. After subcutaneous rIL 2 therapy, a slight increase in the percentage of NK cells expressing only the p75 IL‐2R was shown. CD3+ lympho cytes still retained the p75 IL‐2R negative phenotype, however, with a significant increase (> 15%) in p55 IL‐2R expression. The absolute number of CD3+ lymphocytes was also significantly increased. Functional tests on the purified CD3+ population indicate that these cells exhibited low values of cytotoxic and proliferative activities in vitro. Conclusions. The authors' data point out that subcutaneous administration of rIL‐2 during a week period is associated with a marked increase in T‐cells that bear the low affinity p55 IL‐2R. These findings could be relevant considering the independent role of lymphokine modulation mediated by the p55 and p75 IL‐2R on T‐ and NK cells.

Original languageEnglish
Pages (from-to)2562-2569
Number of pages8
JournalCancer
Volume74
Issue number9
DOIs
StatePublished - 1 Nov 1994
Externally publishedYes

Keywords

  • CD3+ lymphocytes
  • IL‐2 receptors
  • natural killer cells
  • rIL‐2 therapy

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