Murine thymic nurse cell clone supports the growth of fetal thymocytes in the presence of interleukin 2

Hideyuki Doi, Satoshi Nakagawa, Masahiro Hata, Shigeru Kasahara, Tsunetoshi Itoh, Tsuneaki Sakata, Ryuji Suzuki, Kinya Nagata, Kazuo Sugamura, Masanobu Nanno

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11 Citations (Scopus)

Abstract

To investigate the role of thymic nurse cells (TNC) in activation and differentiation of fetal CD4CD8 (double‐negative) thymocytes, we have co‐cultured murine fetal thymocytes (14–15 days of gestation) with an established murine TNC clone. We show here that TNC induced the growth of the fetal double‐negative thymocytes in the presence of recombinant interleukin 2 (rIL2). Activated fetal thymocytes markedly formed lymphocyte‐TNC complexes and proliferated extensively after 5 days in the co‐culture. The activated fetal thymocytes in this co‐culture condition remained double negative after 10 days in culture. None of them gave rise to phenotypically and functionally competent lymphocytes during this period. TNC alone and the supernatant of TNC had no effect on activation. The presence of both TNC and rIL2 was necessary for the growth of fetal thymocytes in our system. The proliferation of fetal thymocytes was inhibited by a monoclonal antibody against mouse IL2 receptors (IL2R). The fetal thymocytes could be maintained further in this co‐culture condition. The prolonged cultivation of fetal thymocytes resulted in the establishment of the fetal thymocyte line and its several clones. CD4 single‐positive cells of activated fetal thymocytes first appeared 14 days after the onset of culture and their number increased, whereas CD8+ cells or CD4CD8 double‐positive cells were not observed. These results indicate that fetal CD4CD8 thymocytes underwent phenotypic change after long periods of culture. All established clones of fetal thymocytes are CD4 single positive showing lymphocyte‐TNC interactions but do not express CD3 complex. Northern blot analysis detected mRNA for the γ T cell receptor, but no messages for the δ, α or β T cell receptor. Chemical cross‐linking of 125I‐labeled IL2 revealed that the 90‐kDa band (presumably considered to be the IL2R β chain) was clearly present in IL2‐responsive fetal clones, whereas freshly isolated day 14–15 fetal thymocytes lacked the band. Taken together, TNC might be involved in the differentiation and /or expansion of murine fetal thymocytes by inducing IL2R β chain, which forms the functional IL2R together with IL2R α chain and CD4, one of the T cell accessory molecules, on the cell surface through direct cell‐cell interaction.

Original languageEnglish
Pages (from-to)783-792
Number of pages10
JournalEuropean Journal of Immunology
Volume21
Issue number3
DOIs
Publication statusPublished - 1991 Mar
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Doi, H., Nakagawa, S., Hata, M., Kasahara, S., Itoh, T., Sakata, T., Suzuki, R., Nagata, K., Sugamura, K., & Nanno, M. (1991). Murine thymic nurse cell clone supports the growth of fetal thymocytes in the presence of interleukin 2. European Journal of Immunology, 21(3), 783-792. https://doi.org/10.1002/eji.1830210335