CD27 instructs CD4+ T cells to provide help for the memory CD8+ T cell response after protein immunization.
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.
Xiao
Yanling
Y
Division of Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Peperzak
Victor
V
Keller
Anna M
AM
Borst
Jannie
J
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002772:Cholera Toxin / Q000276:immunology; D045142:Cross-Priming; D020869:Gene Expression Profiling; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000032:analysis / Q000276:immunology; D007376:Interleukin-2 / Q000032:analysis / Q000276:immunology; D008565:Membrane Proteins / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000276:immunology* / Q000378:metabolism
D007376:Interleukin-2; D008565:Membrane Proteins; C411486:Ms4a4b protein, mouse; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D007371:Interferon-gamma; D010047:Ovalbumin; D002772:Cholera Toxin