Volume 9 Supplement 2
Distinct gene expression profiles associated with the susceptibility of pathogen-specific CD4+ T cells to HIV-1 infection
© Hu et al; licensee BioMed Central Ltd. 2012
Published: 13 September 2012
HIV infection causes the progressive depletion of CD4+ T cells. Contrary to the early loss of CD4 response to opportunistic pathogens like Candida albicans, cytomegalovirus (CMV)-specific CD4 response is persistent when total CD4+ T cell number is low. The mechanism is less clear. Despite considerable knowledge for the impact of HIV infection on total CD4+ T cells and their subsets, little is known about HIV infection of CD4+ T cells of different pathogen/antigen (Ag) specificity.
PBMC from HIV-negative donors were CFSE-labeled and stimulated ex vivo with pathogen-specific antigens including viral (CMV), bacterial (Tetanus Toxoid: TT) and fungal (Candida albicans) antigens. HIV infection of Ag-specific CD4+ T cells was determined by intracellular p24 production in CFSE-low population.
While TT- and Candida-specific CD4+ T cells were permissive, CMV-specific CD4+ T cells are highly resistant to both X4 and R5 HIV independent of coreceptor useage. Quantification of HIV DNA in sorted, antigen-specific CD4+ T cells demonstrated a reduction of both strong-stop and full-length HIV DNA in CMV-specific CD4+ T cells. β-chemokine neutralization enhanced HIV entry and viral replication in TT- and Candida-specific CD4+ T cells, whereas HIV infection in CMV-specific CD4+ T cells remained low despite increased HIV entry by β-chemokine neutralization, suggesting both entry and post-entry HIV restriction in CMV-specific cells. Microarray analysis revealed distinct gene expression profiles that involved selective upregulation of a broad array of antiviral genes in CMV-specific CD4+ T cells, whereas TT- and Candida-specific CD4+ T cells mainly upregulated a Th17 inflammatory response.
Our data suggest a mechanism for the persistence of CMV-specific CD4 response and the earlier loss of mucosal Th17-associated TT- and Candida-specific CD4 response in AIDS patients. The model described is useful in HIV vaccine studies by evaluating the susceptibility of vaccine-specific CD4 responses to HIV infection.
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.