Lymphoid tissue structure and HIV-1 infection: life or death for T cells

Secondary lymphoid tissue (LT) structure facilitates immune responses and maintains homeostasis of T cells through production of survival factors, such as interleukin (IL)-7 that is 'posted' on the stromal fibroblastic reticular cell (FRC) network on which T cells traffic. Here, we examine the pathological changes that occur in LTs during HIV and simian immunodeficiency virus (SIV) infection. Immune activation leads to collagen deposition and loss of the FRC network itself. This decreases access to IL-7 and reduces the major source of IL-7, both of which deplete naïve T cells to limit immune reconstitution with antiretroviral treatment. We discuss the implications of LT structure damage for the timing of antiretroviral therapy and consider the development of adjunctive antifibrotic agents to improve immune reconstitution in HIV infection.