Journal
PLOS PATHOGENS
Volume 14, Issue 4, Pages -Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.ppat.1006973
Keywords
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Categories
Funding
- National Institutes of Health [AI076066, AI118694, AI106481]
- Martin Delaney Collaboratory: Towards an HIV-1 Cure [BEAT: AI126620, DARE: AI096109, A127966]
- Penn CFAR [AI045008]
- amfAR Institute for HIV Cure Research [amfAR 109301]
- UCSF/Gladstone Institute of Virology & Immunology CFAR [P30 AI027763]
- Swedish Research Council [537-2014-6829]
- Karolinska Institutet
- Magnus Bergvall Stiftelse
- Lars Hiertas Stiftelse
- Mexican Government (Comision de Equidad y Genero de las legislaturas LX-LXI, y Comision de Igualdad de Genero de la Legislatura LXII de la H. Camara de Diputados de la Republica Mexicana)
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CD4+ T cells subsets have a wide range of important helper and regulatory functions in the immune system. Several studies have specifically suggested that circulating effector CD4+ T cells may play a direct role in control of HIV replication through cytolytic activity or autocrine beta-chemokine production. However, it remains unclear whether effector CD4+ T cell expressing cytolytic molecules and beta-chemokines are present within lymph nodes (LNs), a major site of HIV replication. Here, we report that expression of beta-chemokines and cytolytic molecules are enriched within a CD4+ T cell population with high levels of the T-box transcription factors T-bet and eomesodermin (Eomes). This effector population is predominately found in peripheral blood and is limited in LNs regardless of HIV infection or treatment status. As a result, CD4+ T cells generally lack effector functions in LNs, including cytolytic capacity and IFN gamma. and beta-chemokine expression, even in HIV elite controllers and during acute/early HIV infection. While we do find the presence of degranulating CD4+ T cells in LNs, these cells do not bear functional or transcriptional effector T cell properties and are inherently poor to form stable immunological synapses compared to their peripheral blood counterparts. We demonstrate that CD4+ T cell cytolytic function, phenotype, and programming in the peripheral blood is dissociated from those characteristics found in lymphoid tissues. Together, these data challenge our current models based on blood and suggest spatially and temporally dissociated mechanisms of viral control in lymphoid tissues.
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