- Oral presentation
- Open Access
Expanded memory CD4+ T Cells in the fetal and the infant Gut; a mucosal route for mother-to-child transmission of HIV-1
© Bunders et al; licensee BioMed Central Ltd. 2012
Published: 13 September 2012
Cord blood-derived CD4+ T cells have a naïve phenotype and do not express CCR5, the mandatory co-receptor for transmitted HIV-1 R5 strains in infants. This leaves the question unanswered: what are the target cells for MTCT of HIV-1 and where do they reside? We hypothesized that in infant mucosal tissues, CD4+CCR5+ T cells may be present to facilitate mucosal transmission of HIV-1.
Using multicolor immuno-histochemistry, flowcytometry and next-generation sequencing of the T cell receptor, we analyzed various human fetal and infant tissues to identify memory CD4+ T cells as targets for HIV-1.
Here, we demonstrate the previously unrecognized abundance of memory CD4+CCR5+ T cells in the human fetal and infant gut mucosa. CD4+ T cells from mesenteric lymph node were mostly naïve, similar to blood. T helper differentiation profiles as determined by transcription factors differed by tissue, with T-bet and RORγt predominantly expressed by memory T cells in the gut mucosa. Next-generation sequencing for high-resolution screening of the T-cell receptor β-chain repertoire of clonal T cells as a hallmark of memory cells, identified expanded T cell clones in the gut mucosa (30%) and not in lymph node or cord blood. The gut mucosal fetal and infant CD4+ T cells were extremely susceptible to HIV-1 without any prestimulation; pol proviral DNA levels were similar to infected PHA stimulated adult PBMCs.
In conclusion, we show that extensive adaptive immunity, with a tissue-depended distribution is present before birth, resulting in the gut mucosa as the preferential site for memory CD4+ T cells. These memory CD4+CCR5+T cells provide a large pool of susceptible cells for ingested HIV-1 at birth and during breastfeeding, indicating a mucosal route of MTCT of HIV-1, which can be targeted in future prevention strategies.
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.