Dendritic cells (DCs), because they orchestrate the immune response to microbes, represent an ideal target for pathogens attempting to evade the immune system. We hypothesized that interactions between human immunodeficiency virus (HIV) and DCs lead to the development of a semimature state, in which DCs migrate to lymph nodes but induce tolerance in T cells, rather than immunity. We found that lymph nodes from untreated HIV-infected subjects contained an abundance of semimature DCs, the disappearance of which correlated with the initiation of highly active antiretroviral therapy (HAART). Such lymph nodes also contained an abundance of T cells that had a regulatory phenotype and that persisted after HAART. Lymph node DCs from untreated HIV-infected subjects cultured with normal allogeneic T cells induced these T cells to adopt the phenotype of regulatory T cells, an ability that was lost after HAART. We conclude that HIV infection correlates with the presence of semimature DCs that stimulate T cell tolerance rather than immunity. These regulatory T cells may contribute to the lack of effective HIV immune responses.
Bibliographical noteFunding Information:
Received 8 March 2005; accepted 1 September 2005; electronically published 19 January 2006 Potential conflicts of interest: none reported. Financial support: National Institutes of Health (grant AI-015441. , Present affiliation: Rosetta Stone Labs, Indianapolis, Indiana. Reprints or correspondence: Dr. Mitchell Krathwohl, Rosetta Stone Labs, 9126 Prairie Ridge PI., Indianapolis, IN 46256 (firstname.lastname@example.org The Journal of Infectious Diseases 2006;193:494-504 © 2006 by the Infectious Diseases Society of America. All rights reserved. 0022-1899/2006/19304-0004$1500