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Generation of Induced Regulatory T Cells from Primary Human Naïve and Memory T Cells
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Published on: April 16, 2012

Cytokine-driven proliferation and differentiation of human naïve, central memory and effector memory CD4+ T cells

J Geginat1, F Sallusto, A Lanzavecchia

  • 1Institute for research in biomedicine, Via Vincenzo Vela 6, 6500, Bellinzona, Suisse. jens.geginat@irb.unisi.ch <jens.geginat@irb.unisi.ch>

Pathologie-Biologie
|June 13, 2003
PubMed

Insights

Memory T cells, crucial for immunity, can divide without antigen. Cytokines like IL-7 and IL-15 promote the expansion of effector memory T cells (T(EM)) from central memory T cells (T(CM)).

Area of Science:

  • Immunology
  • Cell Biology
  • T lymphocyte research

Background:

  • Memory T lymphocytes maintain immune surveillance through continuous division in vivo, independent of antigen exposure.
  • Central memory (T(CM)) and effector memory T cells (T(EM)) possess distinct functional and homing characteristics, contributing to a diverse immune repertoire.
  • Cytokines play a critical role in regulating T cell homeostasis and proliferation.

Purpose of the Study:

  • To investigate the differential proliferative responses of human CD4+ naive T cells, T(CM), and T(EM) to various cytokines.
  • To elucidate the mechanisms by which dendritic cell (DC)-derived cytokines influence T cell proliferation and differentiation.
  • To explore the potential for antigen-independent generation of effector memory T cells from central memory T cells.

Main Methods:

  • Comparative analysis of human CD4+ naive T, T(CM), and T(EM) cell proliferation in response to specific cytokines (IL-7, IL-15, IL-4).
  • Assessment of cytokine-driven proliferation using signaling pathway inhibitors (ERK, p38 MAP kinases).
  • Ex vivo BrdU incorporation assays to confirm in vivo proliferation of memory T cells under steady-state conditions.

Main Results:

  • Interleukin-7 (IL-7) and IL-15 significantly expanded T(EM) cells, with T(CM) showing a lesser response and naive T cells none.
  • Dendritic cell-derived cytokines modulated naive T cell responses to IL-4 and enhanced T(CM) responses to IL-7/IL-15 by upregulating IL-2/IL-15Rss and gamma(c) expression.
  • Cytokine-driven proliferation in T(CM) led to the acquisition of effector functions and non-lymphoid tissue homing capacity, with both T(CM) and T(EM) proliferating in vivo.

Conclusions:

  • Cytokines are key drivers of memory T cell proliferation and differentiation, independent of antigen.
  • A mechanism for sustained, antigen-independent generation of T(EM) from T(CM) cells is proposed, contributing to immune memory maintenance.
  • These findings offer insights into the maintenance of a functionally diverse human CD4+ memory T cell repertoire.

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