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HIV-1 Tat addresses dendritic cells to induce a predominant Th1-type adaptive immune response that appears prevalent in the asymptomatic stage of infection.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2009 Mar 01; Vol. 182 (5), pp. 2888-97. - Publication Year :
- 2009
-
Abstract
- Tat is an early regulatory protein that plays a major role in human HIV-1 replication and AIDS pathogenesis, and therefore, it represents a key target for the host immune response. In natural infection, however, Abs against Tat are produced only by a small fraction (approximately 20%) of asymptomatic individuals and are rarely seen in progressors, suggesting that Tat may possess properties diverting the adaptive immunity from generating humoral responses. Here we show that a Th1-type T cell response against Tat is predominant over a Th2-type B cell response in natural HIV-1 infection. This is likely due to the capability of Tat to selectively target and very efficiently enter CD1a-expressing monocyte-derived dendritic cells (MDDC), which represent a primary target for the recognition and response to virus Ag. Upon cellular uptake, Tat induces MDDC maturation and Th1-associated cytokines and beta-chemokines production and polarizes the immune response in vitro to the Th1 pattern through the transcriptional activation of TNF-alpha gene expression. This requires the full conservation of Tat transactivation activity since neither MDDC maturation nor TNF-alpha production are found with either an oxidized Tat, which does not enter MDDC, or with a Tat protein mutated in the cysteine-rich region (cys22 Tat), which enters MDDC as the wild-type Tat but is transactivation silent. Consistently with these data, inoculation of monkeys with the native wild-type Tat induced a predominant Th1 response, whereas cys22 Tat generated mostly Th2 responses, therefore providing evidence that Tat induces a predominant Th1 polarized adaptive immune response in the host.
- Subjects :
- AIDS Vaccines administration & dosage
AIDS Vaccines immunology
Adult
Aged
Animals
Cells, Cultured
Chemokines, CC biosynthesis
Cytokines biosynthesis
Dendritic Cells metabolism
Female
HIV Antibodies biosynthesis
HIV Infections prevention & control
HeLa Cells
Humans
Immunity, Innate
Macaca fascicularis
Male
Middle Aged
Monocytes immunology
Monocytes virology
T-Lymphocytes, Cytotoxic immunology
T-Lymphocytes, Cytotoxic virology
Th1 Cells metabolism
tat Gene Products, Human Immunodeficiency Virus administration & dosage
tat Gene Products, Human Immunodeficiency Virus immunology
Dendritic Cells immunology
Dendritic Cells virology
HIV Infections immunology
HIV Infections pathology
HIV-1 immunology
Th1 Cells immunology
Th1 Cells virology
tat Gene Products, Human Immunodeficiency Virus physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1550-6606
- Volume :
- 182
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 19234184
- Full Text :
- https://doi.org/10.4049/jimmunol.0711406