TY - JOUR
T1 - T cell dynamics in HIV-1 infection
AU - Douek, Daniel C.
AU - Picker, Louis J.
AU - Koup, Richard A.
PY - 2003
Y1 - 2003
N2 - In the absence of antiretroviral treatment, HIV-1 establishes a chronic, progressive infection of the human immune system that invariably, over the course of years, leads to its destruction and fatal immunodeficiency. Paradoxically, while viral replication is extensive throughout the course of infection, deterioration of conventional measures of immunity is slow, including the characteristic loss of CD4+ T cells that is thought to play a key role in the development of immunodeficiency. This conundrum suggests that CD4+ T cell-directed viral cytopathicity alone cannot explain the course of disease. Indeed, recent advances now indicate that HIV-1 pathogenesis is likely to result from a complex interplay between the virus and the immune system, particularly the mechanisms responsible for T cell homeostasis and regeneration. We review these data and present a model of HIV-1 pathogenesis in which the protracted loss of CD4+ T cells results from early viral destruction of selected memory T cell populations, followed by a combination of profound increases in overall memory T cell turnover, damage to the thymus and other lymphoid tissues, and physiological limitations in peripheral CD4+ T cell renewal.
AB - In the absence of antiretroviral treatment, HIV-1 establishes a chronic, progressive infection of the human immune system that invariably, over the course of years, leads to its destruction and fatal immunodeficiency. Paradoxically, while viral replication is extensive throughout the course of infection, deterioration of conventional measures of immunity is slow, including the characteristic loss of CD4+ T cells that is thought to play a key role in the development of immunodeficiency. This conundrum suggests that CD4+ T cell-directed viral cytopathicity alone cannot explain the course of disease. Indeed, recent advances now indicate that HIV-1 pathogenesis is likely to result from a complex interplay between the virus and the immune system, particularly the mechanisms responsible for T cell homeostasis and regeneration. We review these data and present a model of HIV-1 pathogenesis in which the protracted loss of CD4+ T cells results from early viral destruction of selected memory T cell populations, followed by a combination of profound increases in overall memory T cell turnover, damage to the thymus and other lymphoid tissues, and physiological limitations in peripheral CD4+ T cell renewal.
KW - Activation
KW - Lymphopenia
KW - T cells
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U2 - 10.1146/annurev.immunol.21.120601.141053
DO - 10.1146/annurev.immunol.21.120601.141053
M3 - Review article
C2 - 12524385
AN - SCOPUS:0041888480
SN - 0732-0582
VL - 21
SP - 265
EP - 304
JO - Annual review of immunology
JF - Annual review of immunology
ER -