Analysis of IL-2, IL-4 and their receptors in clonally-related cell lines derived from a patient with a progressive cutaneous T-cell lymphoproliferative disorder

Mariusz A. Wasik, David C. Seldin, Janet R. Butmarc, Robert Gertz, Rosa Marti, Wlodzimierz Maslinski, Marshall E. Kadin

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16 Scopus citations

Abstract

Three clonally related T-cell lymphoma lines (PB-1, 2A, and 2B) were examined for expression of IL-2, IL-4, and their receptors. All three lines were derived from a single patient who had an atypical, progressive T-cell lymphoproliferative disorder involving primarily skin (Davis, T.H. et al. 1992, N. Engl. J. Med. 326:1115). The PB-1 cell line was obtained from a relatively early, clinically indolent stage of the cutaneous lymphoma, whereas the 2A and 2B lines were established from a late, aggressive stage of the lymphoma. Reverse-transcriptase PCR performed with primer pairs specific for IL-2 and IL-4 showed that no mRNA coding for these cytokines was present in any of the lines with the exception of IL-4 mRNA in the 2A line. No IL-4 protein, however, was found in any of the cell lines including 2A by immunocytochemical staining with anti-IL-4 mAb. Accordingly, no bioactive IL-4 was present in the supernatants of these lines. In contrast, all three T-cell lymphoma lines contained mRNA for IL-2R alpha, IL-2R beta, IL-4R and common gamma chain. Immunocytochemical analysis revealed that only the PB-1 line stained strongly with mAbs specific for IL-2R alpha, IL-2R beta, and IL-4R whereas the 2A and 2B lines showed only limited staining with these mAbs. In contrast to expression of IL-2R alpha and IL-4R primarily on the cell surface, IL-2R beta was localized mainly in the cell cytoplasm. Testing supernatants of the cell lines by ELISA for the presence of soluble alpha chain of the IL-2R (sIL-2R) has shown that only PB-1 secreted a large amount of sIL-2R, whereas the 2A and 2B lines secreted lesser amounts. Furthermore, the PB-1 cells expressed a relatively large number of IL-4R as determined by IL-4 binding studies using an IL-4-alkaline phosphatase fusion protein. The remaining two lines displayed only limited binding of IL-4. Addition of IL-2 and/or IL-4 to the culture medium did not modulate growth of PB-1 and the other two lines. These findings may indicate that at least some types of T-cell lymphoma evolve from cells which lose the capacity to synthesize T-cell autocrine growth factors such as IL-2 and IL-4, and show progressive loss of receptors for these cytokines.

Original languageEnglish
Pages (from-to)125-136
Number of pages12
JournalLeukemia and Lymphoma
Volume23
Issue number1-2
DOIs
StatePublished - 1996

Keywords

  • Antigens, CD/biosynthesis
  • Clone Cells/chemistry
  • Cytokines/genetics
  • Disease Progression
  • Humans
  • Immunohistochemistry
  • Interleukin-2/biosynthesis
  • Interleukin-4/biosynthesis
  • Lymphoma, T-Cell/metabolism
  • RNA, Messenger/biosynthesis
  • Receptors, Interleukin-2/biosynthesis
  • Receptors, Interleukin-4
  • Receptors, Interleukin/biosynthesis
  • Skin Neoplasms/metabolism
  • Solubility

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