In vivo analysis of Fas/FasL interactions in HIV-infected patients.
Recent insights into the pharmacological control of HIV replication and the molecular mechanisms of peripheral T cells homeostasis allowed us to investigate in vivo the mechanisms mediating T cell depletion in HIV-infected patients. Before the initiation of highly active antiretroviral therapy (HAART), a high degree of lymphoid tissue apoptosis is present, which is reduced upon HAART initiation (P < 0.001) and directly correlates with reduction of viral load and increases of peripheral T lymphocytes (P < 0.01). Because Fas/FasL interactions play a key role in peripheral T lymphocyte homeostasis, we investigated the susceptibility to Fas-mediated apoptosis in peripheral T lymphocytes and of FasL expression in lymphoid tissue before and during HAART. High levels of Fas-susceptibility found in peripheral CD4 T lymphocytes before HAART were significantly reduced after HAART, coinciding with decreases in viral load (P = 0.018) and increases in peripheral CD4 T lymphocyte counts (P < 0.01). However, the increased FasL expression in the lymphoid tissue of HIV-infected individuals was not reduced after HAART. These results demonstrate that lymphoid tissue apoptosis directly correlates with viral load and peripheral T lymphocyte numbers, and suggest that HIV-induced susceptibility to Fas-dependent apoptosis may play a key role in the regulation of T cell homeostasis in HIV-infected individuals.
Badley
A D
AD
Department of Immunology, Mayo Clinic, Rochester, Minnesota 55905, USA.
Dockrell
D H
DH
Algeciras
A
A
Ziesmer
S
S
Landay
A
A
Lederman
M M
MM
Connick
E
E
Kessler
H
H
Kuritzkes
D
D
Lynch
D H
DH
Roche
P
P
Yagita
H
H
Paya
C V
CV
D019380:Anti-HIV Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D018791:CD4 Lymphocyte Count; D053222:Fas Ligand Protein; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D006801:Humans; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000378:metabolism*; D013601:T-Lymphocytes / Q000187:drug effects / Q000502:physiology; D019014:fas Receptor / Q000378:metabolism*
D019380:Anti-HIV Agents; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D019014:fas Receptor