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Infection and Immunity, August 2004, p. 4455-4463, Vol. 72, No. 8
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.8.4455-4463.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

CD4+ Th1 Cells Induced by Dendritic Cell-Based Immunotherapy in Mice Chronically Infected with Leishmania amazonensis Do Not Promote Healing

Yannick F. Vanloubbeeck,1 Amanda E. Ramer,2 Fei Jie,2 and Douglas E. Jones1,2*

Department of Veterinary Pathology, College of Veterinary Medicine,1 Immunobiology Program, Iowa State University, Ames, Iowa 50011-12502

Received 12 March 2004/ Returned for modification 18 April 2004/ Accepted 9 May 2004

The susceptibility of mice to Leishmania amazonensis infection is thought to result from an inability to develop a Th1 response. Our data show that the low levels of gamma interferon (IFN-{gamma}) produced by the draining lymph node (DLN) cells of chronically infected mice could be enhanced in vitro and in vivo with L. amazonensis antigen-pulsed bone marrow-derived dendritic cells (BM-DC) and the Th1-promoting cytokine interleukin-12 (IL-12). Given intralesionally to chronically infected mice, this treatment induced the upregulation of mRNA levels for IFN-{gamma}, the transcription factor T-box expressed in T cells, and IL-12 receptor ß2 in CD4+ T cells from the DLN and an increase in parasite-specific immunoglobulin G2a in the serum. However, this Th1 response was not associated with healing, and the antigen-specific enhancement of IFN-{gamma} production remained impaired in the DLN. However, addition of IL-12 to the in vitro recall response was able to recover this defect, suggesting that antigen-presenting cell-derived IL-12 production may be limited in infected mice. This was supported by the fact that L. amazonensis amastigotes limited the production of IL-12p40 from BM-DC in vitro. Altogether, our data indicate that the immune response of mice chronically infected with L. amazonensis can be enhanced towards a Th1 phenotype but that the presence of Th1 CD4+ T cells does not promote healing. This suggests that the phenotype of the CD4+ T cells may not always be indicative of protection to L. amazonensis infection. Furthermore, our data support growing evidence that antigen-presenting cell function, such as IL-12 production, may limit the immune response in L. amazonensis-infected mice.

* Corresponding author. Mailing address: Department of Veterinary Pathology 2750, College of Veterinary Medicine, Iowa State University, Ames, IA 50011-1250. Phone: (515) 294-3282. Fax: (515) 294-5423. E-mail: jonesdou{at}iastate.edu.

Editor: W. A. Petri, Jr.

Infection and Immunity, August 2004, p. 4455-4463, Vol. 72, No. 8
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.8.4455-4463.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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