The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1998/9/1075/ $5.00
The Journal of Experimental Medicine, Volume 188, Number 6, September 21, 1998 1075-1082

Articles

Predominant Role for Directly Transfected Dendritic Cells in Antigen Presentation to CD8+ T Cells after Gene Gun Immunization

Angel Porgador*, Kari R. Irvine{ddagger}, Akiko Iwasaki§, Brian H. Barber§, Nicholas P. Restifo{ddagger}, and Ronald N. Germain*

From the * Lymphocyte Biology Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, and the {ddagger} Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-1892; and the § Department of Immunology, University of Toronto, Toronto, Ontario, M5S 1A8, Canada

Cutaneous gene (DNA) bombardment results in substantial expression of the encoded antigen in the epidermal layer as well as detectable expression in dendritic cells (DC) in draining lymph nodes (LNs). Under these conditions, two possible modes of DC antigen presentation to naive CD8+ T cells might exist: (a) presentation directly by gene-transfected DC trafficking to local lymph nodes, and (b) cross-presentation by untransfected DC of antigen released from or associated with transfected epidermal cells. The relative contributions of these distinct modes of antigen presentation to priming for cytotoxic T cell (CTL) responses have not been clearly established. Here we show that LN cells directly expressing the DNA-encoded antigen are rare; 24 h after five abdominal skin bombardments, the number of these cells does not exceed 50–100 cells in an individual draining LN. However, over this same time period, the total number of CD11c+ DC increases more than twofold, by an average of 20,000–30,000 DC per major draining node. This augmentation is due to gold bombardment and is independent of the presence of plasmid DNA. Most antigen-bearing cells in the LNs draining the site of DNA delivery appear to be DC and can be depleted by antibodies to an intact surface protein encoded by cotransfected DNA. This finding of predominant antigen presentation by directly transfected cells is also consistent with data from studies on cotransfection with antigen and CD86-encoding DNA, showing that priming of anti-mutant influenza nucleoprotein CTLs with a single immunization is dependent upon coexpression of the DNAs encoding nucleoprotein and B7.2 in the same cells. These observations provide insight into the relative roles of direct gene expression and cross-presentation in CD8+ T cell priming using gene gun immunization, and indicate that augmentation of direct DC gene expression may enhance such priming.

Key Words: dendritic cells • DNA immunization • cytotoxic T lymphocytes • gene gun • antigen presentation

Address correspondence to Ronald N. Germain, Laboratory of Immunology, Bldg. 10, Rm. 11N311, 10 Center Dr. MSC-1892, Bethesda, MD 20892-1892. Phone: 301-496-1904; Fax: 301-496-0222; E-mail: ronald_germain{at}nih.gov

A. Porgador and K.R. Irvine contributed equally to this paper.

Abbreviations used: DC, dendritic cell(s); GFP, green fluorescent protein; NP, nucleoprotein.


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