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Induction of CD70 on Dendritic Cells through CD40 or TLR Stimulation Contributes to the Development of CD8+ T Cell Responses in the Absence of CD4+ T Cells
| Content Provider | Scilit |
|---|---|
| Author | Bullock, Timothy N. J. Yagita, Hideo |
| Copyright Year | 2005 |
| Description | The expansion of $CD8^{+}$ T cells in response to Ag can be characterized as either dependent or independent of $CD4^{+}$ T cells. The factors that influence this dichotomy are poorly understood but may be dependent upon the degree of inflammation associated with the Ag. Using dendritic cells derived from MHC class II-deficient mice to avoid interaction with $CD4^{+}$ T cells in vivo, we have compared the immunogenicity of peptide-pulsed dendritic cells stimulated with molecules associated with infection to those stimulated via CD40. In the absence of $CD4^{+}$ T cell help, the expansion of primary $CD8^{+}$ T cells after immunization with TNF-α- or poly(I:C)-stimulated dendritic cells was minimal. In comparison, LPS- or CpG-stimulated dendritic cells elicited substantial primary $CD8^{+}$ T cell responses, though not to the same magnitude generated by immunization with CD40L-stimulated dendritic cells. Remarkably, mice immunized with any stimulated dendritic cell population generated fully functional recall $CD8^{+}$ T cells without the aid of $CD4^{+}$ T cell help. The observed hierarchy of immunogenicity was closely correlated with the expression of CD70 (CD27L) on the stimulated dendritic cells, and Ab-mediated blockade of CD70 substantially prevented the $CD4^{+}$ T cell-independent expansion of primary $CD8^{+}$ T cells. These results indicate that the expression of CD70 on dendritic cells is an important determinant for helper-dependence of primary $CD8^{+}$ T cell expansion and provide an explanation for the ability of a variety of pathogens to stimulate primary $CD8^{+}$ T cell responses in the absence of $CD4^{+}$ T cells. |
| Ending Page | 717 |
| Page Count | 8 |
| Starting Page | 710 |
| ISSN | 00221767 |
| e-ISSN | 15506606 |
| DOI | 10.4049/jimmunol.174.2.710 |
| Journal | The Journal of Immunology |
| Issue Number | 2 |
| Volume Number | 174 |
| Language | English |
| Publisher | The American Association of Immunologists |
| Publisher Date | 2005-01-15 |
| Access Restriction | Open |
| Subject Keyword | Dendritic Cells Stimulated Dendritic Primary Cd8 Cell Expansion |
| Content Type | Text |
| Resource Type | Article |
| Subject | Immunology and Allergy Immunology |
