CD4+ T cells are required for the maintenance, not programming, of memory CD8+ T cells after acute infection

Nat Immunol. 2004 Sep;5(9):927-33. doi: 10.1038/ni1105. Epub 2004 Aug 8.


Immunization in the absence of CD4(+) T cell help results in defective CD8(+) T cell memory, deficient recall responses and diminished protective immunity. Here we investigated at what stage during the immune response to pathogen CD4(+) T cells are essential in the promotion of functional CD8(+) T cell memory. Memory CD8(+) T cell numbers decreased gradually in the absence of CD4(+) T cells despite the presence of similar numbers of memory cell precursors at the peak of the effector phase. Adoptive transfer of effector or memory CD8(+) T cells into wild-type or CD4(+) T cell-deficient mice demonstrated that the presence of CD4(+) T cells was important only after, not during, the early CD8(+) T cell programming phase. In the absence of CD4(+) T cells, memory CD8(+) T cells became functionally impaired and decreased in quantity over time. We conclude that in the context of an acute infection, CD4(+) T cells are required only during the maintenance phase of long-lived memory CD8(+) T cells.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adoptive Transfer
  • Animals
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Histocompatibility Antigens Class II
  • Immunologic Memory*
  • Listeria monocytogenes / immunology
  • Lymphocyte Activation / immunology*
  • Lymphocytic choriomeningitis virus / immunology
  • Mice
  • Mice, Transgenic
  • Receptors, Interleukin-7 / biosynthesis
  • Receptors, Interleukin-7 / immunology


  • Histocompatibility Antigens Class II
  • Receptors, Interleukin-7
  • interleukin-7 receptor, alpha chain