Collagen deposition and loss of the FRC network impede access to and source of IL-7 in HIV-1 infection.

A. FRCs are the major producers of IL-7. LN sections (representative image for one HIV negative subject of 5) stained for desmin (red) and IL-7 (green). Merged confocal image shows co-localization of IL-7 and FRCs in T cell area. Scale bar, 10 µm. B–C. Collagen deposition and loss of the FRC network disrupts interaction between T cells and FRCs. Confocal images of LN sections from an uninfected subject (representative image for one subject of 5) immunofluorescently stained for desmin (green), collagen (red) and CD3 (blue). The merged image shows that FRCs colocalize with collagen and T cells are in contact with the FRC network (B). Confocal images of LN sections from a subject at AIDS stage (representative image for one subject of 6). The merged image shows that the loss of FRCs and associated collagen deposition leads to loss of the contact between FRCs and T cells, which instead contact mainly extra-FRC collagen. Scale bar, 20 µm (C). D. Confocal images of LN sections from HIV negative subjects and from subjects at different stage of HIV infection immunofluorescently stained for desmin (green) and collagen (red), showing the gradual loss of FRCs in the T cell zone within LTs, which is associated with extensive collagen deposition during HIV infection. Scale bar, 20 µm. E. Quantification of average amount of FRCs and collagen deposition at each stage of infection, showing the gradual loss of FRCs and collagen deposition. Error bars represent the s.d. F. Confocal images of LN sections from HIV negative subjects and from subjects at different stage of HIV infection immunofluorescently stained for IL-7 (green), showing that the gradual loss of IL-7 in the T cell zone is associated with gradual depletion of FRCs (E). Scale bar, 20 µm.