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CD27 Instructs CD4⁺ T Cells to Provide Help for the Memory CD8⁺ T Cell Response after Protein Immunization¹

Division of Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands

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-- 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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by grants from The Netherlands Organization for Scientific Research and the Dutch Cancer Society.

² Y.X. and V.P. contributed equally to this work.

³ Address correspondence and reprint requests to Dr. Jannie Borst, Division of Immunology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands. E-mail address: j.borst{at}nki.nl

⁴ Abbreviations used in this paper: DC, dendritic cells; CT, cholera toxin; DLN, draining lymph nodes; MFI, mean fluorescence intensity; WT, wild type.

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The JI 2008 181: 855-856. [Full Text]  

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