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Infection and Immunity, January 2003, p. 68-74, Vol. 71, No. 1
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.1.68-74.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Effects of Tumor Necrosis Factor Alpha on Dendritic Cell Accumulation in Lymph Nodes Draining the Immunization Site and the Impact on the Anticryptococcal Cell-Mediated Immune Response

Sean K. Bauman,1 Gary B. Huffnagle,2 and Juneann W. Murphy1*

Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73190,1 Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, Michigan 481092

Received 24 June 2002/ Returned for modification 4 September 2002/ Accepted 19 September 2002

Cell-mediated immune (CMI) responses and tumor necrosis factor alpha (TNF-{alpha}) have been shown to be essential in acquired protection against Cryptococcus neoformans. Induction of a protective anticryptococcal CMI response includes increases in dendritic cells (DC) and activated CD4+ T cells in draining lymph nodes (DLN). During the expression phase, activated CD4+ T cells accumulate at a peripheral site where cryptococcal antigen is injected, resulting in a classical delayed-type hypersensitivity (DTH) reaction. Induction of a nonprotective anticryptococcal CMI response results in no significant increases in the numbers of DC or activated CD4+ T cells in DLN. This study focuses on examining the role of TNF-{alpha} in induction of protective and nonprotective anticryptococcal CMI responses. We found that neutralization of TNF-{alpha} at the time of immunization with the protective immunogen (i) reduces the numbers of Langerhans cells, myeloid and lymphoid DC, and activated CD4+ T cells in DLN and (ii) diminishes the total numbers of cells, the numbers of activated CD4+ T cells, and amount of gamma interferon at the DTH reaction site. Although TNF-{alpha} neutralization during induction of the nonprotective CMI response had little effect on cellular and cytokine parameters measured, it did cause a reduction in footpad swelling when mice received challenge in the footpad. Our findings show that TNF-{alpha} functions during induction of the protective CMI response by influencing the accumulation of all three DC subsets into DLN. Without antigen stimulated DC in DLN, activated CD4+ T cells are not induced and thus not available for the expression phase of the CMI response.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, P. O. Box 26901, BMSB 1053, Oklahoma City, OK 73190. Phone (405) 271-3110. Fax: (405) 271-3117. E-mail: juneann-murphy{at}ouhsc.edu.

Editor: T. R. Kozel

Infection and Immunity, January 2003, p. 68-74, Vol. 71, No. 1
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.1.68-74.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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