TY - JOUR
T1 - Lymphatic tissue fibrosis is associated with reduced numbers of naïve CD4+ T cells in human immunodeficiency virus type 1 infection
AU - Schacker, Timothy W.
AU - Brenchley, Jason M.
AU - Beilman, Gregory J.
AU - Reilly, Cavan
AU - Pambuccian, Stefan E.
AU - Taylor, Jodie
AU - Skarda, David
AU - Larson, Matthew
AU - Douek, Daniel C.
AU - Haase, Ashley T.
PY - 2006/5
Y1 - 2006/5
N2 - The organized structure of lymphatic tissues (LTs) constitutes a microenvironment referred to as a niche that plays a critical role in immune system homeostasis by promoting cellular interactions and providing access to cytokines and growth factors on which cells are dependent for survival, proliferation, and differentiation. In chronic human immunodeficiency virus type 1 (HIV-1) infection, immune activation and inflammation result in collagen deposition and disruption of this LT niche. We have previously shown that these fibrotic changes correlate with a reduction in the size of the total population of CD4+ T cells. We now show that this reduction is most substantial within the naïve CD4+ T-cell population and is in proportion to the extent of LT collagen deposition in HIV-1 infection. Thus, the previously documented depletion of naïve CD4+ T cells in LTs in HIV-1 infection may be a consequence not only of a decreased supply of thymic emigrants or chronic immune activation but also of the decreased ability of those cells to survive in a scarred LT niche. We speculate that LT collagen deposition might therefore limit repopulation of naïve CD4+ T cells with highly active antiretroviral therapy, and thus, additional treatments directed to limiting or reversing inflammatory damage to the LT niche could potentially improve immune reconstitution.
AB - The organized structure of lymphatic tissues (LTs) constitutes a microenvironment referred to as a niche that plays a critical role in immune system homeostasis by promoting cellular interactions and providing access to cytokines and growth factors on which cells are dependent for survival, proliferation, and differentiation. In chronic human immunodeficiency virus type 1 (HIV-1) infection, immune activation and inflammation result in collagen deposition and disruption of this LT niche. We have previously shown that these fibrotic changes correlate with a reduction in the size of the total population of CD4+ T cells. We now show that this reduction is most substantial within the naïve CD4+ T-cell population and is in proportion to the extent of LT collagen deposition in HIV-1 infection. Thus, the previously documented depletion of naïve CD4+ T cells in LTs in HIV-1 infection may be a consequence not only of a decreased supply of thymic emigrants or chronic immune activation but also of the decreased ability of those cells to survive in a scarred LT niche. We speculate that LT collagen deposition might therefore limit repopulation of naïve CD4+ T cells with highly active antiretroviral therapy, and thus, additional treatments directed to limiting or reversing inflammatory damage to the LT niche could potentially improve immune reconstitution.
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U2 - 10.1128/CVI.13.5.556-560.2006
DO - 10.1128/CVI.13.5.556-560.2006
M3 - Article
C2 - 16682476
AN - SCOPUS:33646689587
SN - 1556-6811
VL - 13
SP - 556
EP - 560
JO - Clinical and Diagnostic Laboratory Immunology
JF - Clinical and Diagnostic Laboratory Immunology
IS - 5
ER -