Importance of Follicular Helper T Cells
According to a recent study from the group of Giuseppe Pantaleo, follicular dendritic cells (Tfh) represent the major CD4 T cell compartment for HIV-1 infection, replication and production.The authors show that this cell subset contains the highest number of HIV DNA copies and is also enriched in HIV specific CD4 T cells. They speculate that antibodies targetting this cell subset could reduce the HIV reservoir.
The authors (1) studied different populations of memory CD4 T cells isolated from lymph nodes of:
-23 subjects with chronic HIV infection with CD4 T cell counts >400/mm3 and plasma viremia >5,000 copies/ml;
-14 subjects with undetectable viremia (<20 c/ml) after 72 weeks of ART;
-3 subjects LTNPs and low viremia levels;
-13 HIV negative controls.
Different markers were used to differentiate between cell subsets. The Tfh cells corresponded to the CXCR5+ PD-1+ subset. These cells reside within the germinal centers, express Bcl-6 and have the ability to both produce IL-21 and support Ig production.
The highest number of HIV DNA copies was found in Tfh cells (mean: 50,953 copies/106 mononuclear cells), followed by CXCR5- PD-1+ cells (23,182 copies/106 cells). Previous studies have shown that CXCR5- PD-1+ cells reside outside germinal centers and could contain precursors of Tfh cells.
In vitro experiments confirmed that Tfh cells were the most efficient in supporting both HIV replication and production.
Consequently, Tfh cells appears to be good candidates for supporting residual virus replication and eventually be the origin of viral blips.
The authors conclude that "Development of bi-specific antibodies to CD4 and PD-1 coupled to toxins may represent an effective strategy to purge HIV-infected Tfh and CXCR5- PD-1+ cells".
Perreau M, Savoye AL, De Crignis E et al. Follicular helper T cells serve as the major CD4 T cell compartment for HIV-1 infection, replication and production. J Exp Med 2012, Dec 17, Epub ahead of print
Key words: HIV cure, HIV reservoirs