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Dendritic cell-mediated HIV-1 transmission to T cells of LAD-1 patients is impaired due to the defect in LFA-1

Fedde Groot1,2,4 email, Taco W Kuijpers3 email, Ben Berkhout1 email and Esther C de Jong2 email

Department of Human Retrovirology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands

Department of Cell Biology and Histology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands

Division of Pediatric Hematology, Immunology and Infectious Diseases, Emma Children's Hospital, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands

Present address: The Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom

author email corresponding author email

Retrovirology 2006, 3:75doi:10.1186/1742-4690-3-75

Published: 1 November 2006

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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