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© The Rockefeller University Press, 0022-1007/2000/2/495/ $5.00
The Journal of Experimental Medicine, Volume 191, Number 3, February 7, 2000 495-502

Original Article

TRANCE, a Tumor Necrosis Factor Family Member, Enhances the Longevity and Adjuvant Properties of Dendritic Cells In Vivo

Régis Josiena, Hong-Li Lia, Elizabeth Ingullid, Supria Sarmab,c, Brian R.Wongb, Maria Vologodskaiac, Ralph M. Steinmana, and Yongwon Choib,c
a From the Laboratory of Cellular Physiology and Immunology, The Rockefeller University, New York, New York 10021
b From the Laboratory of Immunology, The Rockefeller University, New York, New York 10021
c From the Howard Hughes Medical Institute, The Rockefeller University, New York, New York 10021
d Department of Pediatrics, University of Minnesota Medical School, Minneapolis, Minnesota 55455

Correspondence to: Ralph M. Steinman, Laboratory of Cellular Physiology and Immunology, The Rockefeller University, 1230 York Ave., 405 Bronk Bldg., New York, NY 10021. Tel:212-327-8106 Fax:212-327-8875 E-mail:steinma{at}rockvax.rockefeller.edu.

Mature dendritic cells (DCs) are powerful antigen presenting cells that have the unique capacity to migrate to the T cell zone of draining lymph nodes after subcutaneous injection. Here we report that treatment of antigen-pulsed mature DCs with tumor necrosis factor (TNF)-related activation-induced cytokine (TRANCE), a TNF family member, before immunization enhances their adjuvant capacity and elicits improved T cell priming in vivo, such that both primary and memory T cell immune responses are enhanced. By enumerating migratory DCs in the draining lymph nodes and by studying their function in stimulating naive T cells, we show that one of the underlying mechanisms for enhanced T cell responses is an increase in the number of ex vivo antigen-pulsed DCs that are found in the T cell areas of lymph nodes. These results suggest that the longevity and abundance of mature DCs at the site of T cell priming influence the strength of the DC-initiated T cell immunity in situ. Our findings have the potential to improve DC-based immunotherapy; i.e., the active immunization of humans with autologous DCs that have been pulsed with clinically significant antigens ex vivo.

Key Words: TRANCE, dendritic cells, T cell, immunization


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