Autocrine IL-2 is required for secondary population expansion of CD8(+) memory T cells

Nat Immunol. 2011 Jul 31;12(9):908-13. doi: 10.1038/ni.2079.


Two competing theories have been put forward to explain the role of CD4(+) T cells in priming CD8(+) memory T cells: one proposes paracrine secretion of interleukin 2 (IL-2); the other proposes the activation of antigen-presenting cells (APCs) via the costimulatory molecule CD40 and its ligand CD40L. We investigated the requirement for IL-2 by the relevant three cell types in vivo and found that CD8(+) T cells, rather than CD4(+) T cells or dendritic cells (DCs), produced the IL-2 necessary for CD8(+) T cell memory. Il2(-/-) CD4(+) T cells were able to provide help only if their ability to transmit signals via CD40L was intact. Our findings reconcile contradictory elements implicit in each model noted above by showing that CD4(+) T cells activate APCs through a CD40L-dependent mechanism to enable autocrine production of IL-2 in CD8(+) memory T cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autocrine Communication*
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • CD40 Antigens / immunology*
  • CD40 Antigens / metabolism
  • CD40 Ligand / immunology*
  • CD40 Ligand / metabolism
  • CD8-Positive T-Lymphocytes* / cytology
  • CD8-Positive T-Lymphocytes* / immunology
  • CD8-Positive T-Lymphocytes* / metabolism
  • Cell Proliferation
  • Dendritic Cells / cytology
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Flow Cytometry
  • Immunologic Memory*
  • Interleukin-2 / immunology*
  • Interleukin-2 / metabolism
  • Listeria monocytogenes / growth & development
  • Listeriosis / immunology
  • Listeriosis / microbiology
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Signal Transduction / immunology


  • CD40 Antigens
  • Interleukin-2
  • CD40 Ligand