Peak SIV replication in resting memory CD4+ T cells depletes gut lamina propria CD4+ T cells
Top Cited Papers
- 27 March 2005
- journal article
- letter
- Published by Springer Science and Business Media LLC in Nature
- Vol. 434 (7037), 1148-1152
- https://doi.org/10.1038/nature03513
Abstract
In early simian immunodeficiency virus (SIV) and human immunodeficiency virus-1 (HIV-1) infections, gut-associated lymphatic tissue (GALT), the largest component of the lymphoid organ system1, is a principal site of both virus production and depletion of primarily lamina propria memory CD4+ T cells; that is, CD4-expressing T cells that previously encountered antigens and microbes and homed to the lamina propria of GALT2,3,4,5,6,7,8,9. Here, we show that peak virus production in gut tissues of SIV-infected rhesus macaques coincides with peak numbers of infected memory CD4+ T cells. Surprisingly, most of the initially infected memory cells were not, as expected10,11, activated but were instead immunophenotypically ‘resting’ cells that, unlike truly resting cells, but like the first cells mainly infected at other mucosal sites and peripheral lymph nodes12,13, are capable of supporting virus production. In addition to inducing immune activation and thereby providing activated CD4+ T-cell targets to sustain infection, virus production also triggered14 an immunopathologically limiting Fas–Fas-ligand-mediated apoptotic pathway15,16 in lamina propria CD4+ T cells, resulting in their preferential ablation. Thus, SIV exploits a large, resident population of resting memory CD4+ T cells in GALT to produce peak levels of virus that directly (through lytic infection) and indirectly (through apoptosis of infected and uninfected cells) deplete CD4+ T cells in the...Keywords
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