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Increasing the Survival of Dendritic Cells In Vivo Does Not Replace the Requirement for CD4⁺ T Cell Help during Primary CD8⁺ T Cell Responses¹

Kate E. Matthews^*, Jim S. Qin^*, Jianping Yang^*, Ian F. Hermans^*,, Michael J. Palmowski, Vincenzo Cerundolo and Franca Ronchese^2,*

^* Malaghan Institute of Medical Research, Wellington, New Zealand; and Tumour Immunology Group, Weatherall Institute of Molecular Medicine, Oxford, United Kingdom

The survival of dendritic cells (DC) in vivo determines the duration of Ag presentation and is critical in determining the strength and magnitude of the resulting T cell response. We used a mouse model to show that Ag-loaded C57BL/6 DC (MHC class II^+/+ (MHC II^+/+)) that reach the lymph node survived longer than Ag-loaded MHC II^–/– DC, with the numbers of C57BL/6 DC being 2.5-fold the number of the MHC II^–/– DC by day 4 and 5-fold by day 7. The differential survival of DC in vivo was not affected by low doses of LPS, but in vitro pretreatment with CD40L or with high doses of LPS increased the numbers of MHC II^–/– DC to levels approaching those of C57BL/6 DC. Regardless of their numbers and relative survival in lymph nodes, MHC II^–/– DC were profoundly defective in their ability to induce CTL responses against the gp33 peptide epitope, and were unable to induce expansion and optimal cytotoxic activity of CD8⁺ T cells specific for the male Ag UTY. We conclude that CD4⁺ T cell help for CD8⁺ responses involves mechanisms other than the increased survival of Ag-presenting DC in the lymph node.

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 a research grant from the Cancer Society of New Zealand and the Health Research Council of New Zealand (to F.R.), and by European Research Grant Cancer Immunotherapy (to V.C.). K.E.M. was supported by a PhD Scholarship from the New Zealand Cancer Institute.

² Address correspondence and reprint requests to Dr. Franca Ronchese, Malaghan Institute of Medical Research, P.O. Box 7060, Wellington South, New Zealand. E-mail address: fronchese{at}malaghan.org.nz

³ Abbreviations used in this paper: DC, dendritic cell; MHC I, MHC class I; MHC II, MHC class II; CTO, Cell Tracker Orange; PI, propidium iodide.

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The JI 2007 179: 5615-5616. [Full Text]  

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