CD27 instructs CD4+ T cells to provide help for the memory CD8+ T cell response after protein immunization

J Immunol. 2008 Jul 15;181(2):1071-82. doi: 10.4049/jimmunol.181.2.1071.


For optimal quality, memory CD8(+) T cells require CD4(+) T cell help. We have examined whether CD4(+) T cells require CD27 to deliver this help, in a model of intranasal OVA protein immunization. CD27 deficiency reduced the capacity of CD4(+) T cells to support Ag-specific CD8(+) T cell accumulation at the tissue site after primary and secondary immunization. CD27-dependent CD4(+) T cell help for the memory CD8(+) T cell response was delivered during priming. It did not detectably affect formation of CD8(+) memory T cells, but promoted their secondary expansion. CD27 improved survival of primed CD4(+) T cells, but its contribution to the memory CD8(+) T cell response relied on altered CD4(+) T cell quality rather than quantity. CD27 induced a Th1-diagnostic gene expression profile in CD4(+) T cells, which included the membrane molecule MS4A4B. Accordingly, CD27 increased the frequency of IFN-gamma- and IL-2-producing CD4(+) T cells. It did not affect CD40L expression. Strikingly, MS4A4B was also identified as a unique marker of CD8(+) memory T cells that had received CD27-proficient CD4(+) T cell help during the primary response. This apparent imprinting effect suggests a role for MS4A4B as a downstream effector in CD27-dependent help for CD8(+) T cell memory.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Cholera Toxin / immunology
  • Cross-Priming
  • Gene Expression Profiling
  • Immunologic Memory*
  • Interferon-gamma / analysis
  • Interferon-gamma / immunology
  • Interleukin-2 / analysis
  • Interleukin-2 / immunology
  • Membrane Proteins / immunology*
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Ovalbumin / immunology
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / immunology*
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / metabolism


  • Interleukin-2
  • Membrane Proteins
  • Ms4a4b protein, mouse
  • Tumor Necrosis Factor Receptor Superfamily, Member 7
  • Interferon-gamma
  • Ovalbumin
  • Cholera Toxin