Abnormal Presence of Semimature Dendritic Cells That Induce Regulatory T Cells in HIV-Infected Subjects

• Published in: The Journal of infectious diseases Vol. 193; no. 4; pp. 494 - 504
• Main Authors: Krathwohl, Mitchell D., Schacker, Timothy W., Anderson, Jodi L.
• Format: Journal Article
• Language: English
• Published: Chicago, IL The University of Chicago Press 15.02.2006; University of Chicago Press; Oxford University Press
• Subjects: Anti-HIV Agents - therapeutic use; Antibodies; Antiretroviral Therapy, Highly Active; Biological and medical sciences; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - pathology; CD4-Positive T-Lymphocytes - virology; Cells, Cultured; Cytometry; Dendritic cells; Dendritic Cells - immunology; Dendritic Cells - metabolism; Dendritic Cells - pathology; Epstein Barr virus infections; Fundamental and applied biological sciences. Psychology; Highly active antiretroviral therapy; HIV; HIV Infections - drug therapy; HIV Infections - immunology; HIV-1 - physiology; HIV/AIDS; Human immunodeficiency virus; Human viral diseases; Humans; Infections; Infectious diseases; Leukocytes, Mononuclear - virology; Lymph nodes; Lymph Nodes - pathology; Lymph Nodes - virology; Medical sciences; Microbiology; Spleen; T lymphocytes; T-Lymphocytes, Regulatory - immunology; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Infection; Immunopathology; Dendritic cell; Microbiology; Viral disease; T-Lymphocyte; AIDS; Immune deficiency
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/499597

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