IL-7 induces proliferation of CD3-/low CD4- CD8- human thymocyte precursors by an IL-2 independent pathway

M Fabbi1, V Groh, J L Strominger

  • 1Department of Biochemistry and Molecular Biology, Harvard University, Cambridge, MA 02138.

International Immunology
|January 1, 1992
PubMed

Insights

Interleukin-7 (IL-7) promotes the in vitro proliferation of human thymocyte precursors, including triple negative and CD3low cells. This growth is independent of the IL-2 pathway, suggesting a significant role for IL-7 in human T cell development.

Area of Science:

  • Immunology
  • Developmental Biology
  • Cell Biology

Background:

  • Human thymocyte precursors, specifically CD3-CD4-CD8- (triple negative) and CD3low(lo)CD4-CD8-, are critical for T cell development.
  • Understanding the cytokine-driven proliferation of these precursors is essential for elucidating T cell ontogeny.

Purpose of the Study:

  • To investigate the proliferation potential of human thymocyte precursors in response to various cytokines.
  • To determine the role of Interleukin-7 (IL-7) and Interleukin-2 (IL-2) in the growth of these precursor cells.

Main Methods:

  • In vitro culture of highly purified human CD3-CD4-CD8- and CD3low(lo)CD4-CD8- thymocyte precursors.
  • Treatment with recombinant human cytokines including IL-2, IL-7, IL-4, and IL-6, with and without phorbol 12-myristate 13-acetate (PMA).
  • Analysis of cell proliferation, IL-2 receptor (IL-2R) p55 expression, and surface phenotype (CD3, CD4, CD8) using flow cytometry.

Main Results:

  • Recombinant human IL-2 (rIL-2) and IL-7 (rIL-7) significantly enhanced in vitro proliferation of thymocyte precursors, both with and without PMA.
  • Proliferation in response to rIL-7 was independent of the autocrine IL-2 pathway, as antibodies to IL-2 and IL-2R p55 did not inhibit rIL-7-mediated growth.
  • rIL-7 synergized with rIL-2, but not with rIL-4 or rIL-6.
  • rIL-7 induced proliferation of both CD3- and CD3low thymocyte precursors, accompanied by upregulation of CD3 antigen expression.

Conclusions:

  • IL-7 is identified as a potent growth factor for human thymocyte precursors, similar to its known roles in pre-B and mature T cells.
  • The proliferative effect of IL-7 on these precursors is independent of the IL-2 pathway, highlighting a distinct mechanism of action.
  • These findings suggest that IL-7 plays a crucial role in human T cell ontogeny, analogous to its function in mouse T cell development.