Abstract:
:Despite potential clinical importance, target cells for mother-to-child transmission of HIV-1 have not yet been identified. Cord blood-derived CD4(+) T cells are largely naive and do not express CCR5, the mandatory coreceptor for transmitted HIV-1 R5 strains in infants. In the present study, we demonstrate that in the human fetal and infant gut mucosa, there is already a large subset of mucosal memory CD4(+)CCR5(+) T cells with predominantly a Th1 and Th17 phenotype. Using next-generation sequencing of the TCRβ chain, clonally expanded T cells as a hallmark for memory development predominated in the gut mucosa (30%), whereas few were found in the lymph nodes (1%) and none in cord blood (0%). The gut mucosal fetal and infant CD4(+) T cells were highly susceptible to HIV-1 without any prestimulation; pol proviral DNA levels were similar to infected phytohemagglutinin-stimulated adult PBMCs. In conclusion, in the present study, we show that extensive adaptive immunity is present before birth and the gut mucosa is the preferential site for memory CD4(+) T cells. These CD4(+)CCR5(+) T cells in the infant mucosa provide a large pool of susceptible cells for ingested HIV-1 at birth and during breastfeeding, indicating a mucosal route of mother-to-child transmission that can be targeted in prevention strategies.
journal_name
Bloodjournal_title
Bloodauthors
Bunders MJ,van der Loos CM,Klarenbeek PL,van Hamme JL,Boer K,Wilde JC,de Vries N,van Lier RA,Kootstra N,Pals ST,Kuijpers TWdoi
10.1182/blood-2012-06-437566subject
Has Abstractpub_date
2012-11-22 00:00:00pages
4383-90issue
22eissn
0006-4971issn
1528-0020pii
blood-2012-06-437566journal_volume
120pub_type
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