TY - JOUR
T1 - Kinetics of CD4+ T cell repopulation of lymphoid tissues after treatment of HIV-1 infection
AU - Zhang, Zhi Qiang
AU - Notermans, Daan W.
AU - Sedgewick, Gerald
AU - Cavert, Winston
AU - Wietgrefe, Stephen
AU - Zupancic, Mary
AU - Gebhard, Kristin
AU - Henry, Keith
AU - Boies, Lawrence
AU - Chen, Zongming
AU - Jenkins, Marc
AU - Mills, Roger
AU - Mcdade, Hugh
AU - Goodwin, Carolyn
AU - Schuwirth, Caspar M.
AU - Danner, Sven A.
AU - Haase, Ashley T.
PY - 1998/2/3
Y1 - 1998/2/3
N2 - Potent combinations of antiretroviral drugs diminish the turnover of CD4+ T lymphocytes productively infected with HIV-1 and reduce the large pool of virions deposited in lymphoid tissue (LT). To determine to what extent suppression of vital replication and reduction in viral antigens in LT might lead correspondingly to repopulation of the immune system, we characterized CD4+ T lymphocyte populations in LT in which we previously had quantitated viral load and turnover of infected cells before and after treatment. We directly measured by quantitative image analysis changes in total CD4+ T cell counts, the CD45RA+ subset, and fractions of proliferating or apoptotic CD4+ T cells. Compared with normal controls, we documented decreased numbers of CD4+ T cells and increased proliferation and apoptosis. After treatment, proliferation returned to normal levels, and total CD4+ T and CD45RA+ cells increased. We discuss the effects of HIV-1 on this subset based on the concept that renewal mechanisms in the adult are operating at full capacity before infection and cannot meet the additional demand imposed by the loss of productively infected cells. The slow increases in the CD45RA+ CD4+ T cells are consistent with the optimistic conclusions that (i) renewal mechanisms have not been damaged irreparably even at relatively advanced stages of infection and (ii) CD4+ T cell populations can be partially restored by control of active replication without eradication of HIV-1.
AB - Potent combinations of antiretroviral drugs diminish the turnover of CD4+ T lymphocytes productively infected with HIV-1 and reduce the large pool of virions deposited in lymphoid tissue (LT). To determine to what extent suppression of vital replication and reduction in viral antigens in LT might lead correspondingly to repopulation of the immune system, we characterized CD4+ T lymphocyte populations in LT in which we previously had quantitated viral load and turnover of infected cells before and after treatment. We directly measured by quantitative image analysis changes in total CD4+ T cell counts, the CD45RA+ subset, and fractions of proliferating or apoptotic CD4+ T cells. Compared with normal controls, we documented decreased numbers of CD4+ T cells and increased proliferation and apoptosis. After treatment, proliferation returned to normal levels, and total CD4+ T and CD45RA+ cells increased. We discuss the effects of HIV-1 on this subset based on the concept that renewal mechanisms in the adult are operating at full capacity before infection and cannot meet the additional demand imposed by the loss of productively infected cells. The slow increases in the CD45RA+ CD4+ T cells are consistent with the optimistic conclusions that (i) renewal mechanisms have not been damaged irreparably even at relatively advanced stages of infection and (ii) CD4+ T cell populations can be partially restored by control of active replication without eradication of HIV-1.
UR - http://www.scopus.com/inward/record.url?scp=13144279356&partnerID=8YFLogxK
U2 - 10.1073/pnas.95.3.1154
DO - 10.1073/pnas.95.3.1154
M3 - Article
C2 - 9448301
AN - SCOPUS:13144279356
SN - 0027-8424
VL - 95
SP - 1154
EP - 1159
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 3
ER -
