Abstract | BACKGROUND: Dendritic cells (DC) have been proposed to mediate sexual HIV-1 transmission by capturing the virus in the mucosa and subsequently presenting it to CD4+ T cells. We have demonstrated before that DC subsets expressing higher levels of intercellular adhesion molecule-1 (ICAM-1) are better HIV-1 transmitters. ICAM-1 binds leukocyte function-associated molecule-1 (LFA-1) on T cells, an integrin responsible for adhesion and signaling at the immunological synapse. To corroborate the importance of the ICAM-1- LFA-1 interaction, we performed transmission experiments to LFA-1 negative leukocytes from Leukocyte Adhesion Deficiency type 1 (LAD-1) patients. RESULTS: We clearly show that DC-mediated HIV-1 transmission to LAD-1 T cells is impaired in comparison to healthy controls. Furthermore, HIV-1 transmission to T cells from a unique LAD-1 patient with a well characterized LFA-1 activation defect was impaired as well, demonstrating that activation of LFA-1 is crucial for efficient transmission. Decreased cell adhesion between DC and LAD-1 T cells could also be illustrated by significantly smaller DC-T cell clusters after HIV-1 transmission. CONCLUSION: By making use of LFA-1 defect cells from unique patients, this study provides more insight into the mechanism of HIV-1 transmission by DC. This may offer new treatment options to reduce sexual transmission of HIV-1.
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Authors | Fedde Groot, Taco W Kuijpers, Ben Berkhout, Esther C de Jong |
Journal | Retrovirology
(Retrovirology)
Vol. 3
Pg. 75
(Nov 01 2006)
ISSN: 1742-4690 [Electronic] England |
PMID | 17078873
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Lymphocyte Function-Associated Antigen-1
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Topics |
- Adolescent
- Child
- Child, Preschool
- Dendritic Cells
(virology)
- Female
- HIV Infections
(transmission, virology)
- HIV-1
(physiology)
- Humans
- Leukocyte-Adhesion Deficiency Syndrome
(immunology, physiopathology, virology)
- Lymphocyte Function-Associated Antigen-1
(metabolism)
- Male
- T-Lymphocytes
(virology)
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