The Fas/FasL system and T cell apoptosis in HIV-1-infected lymphoid tissue during highly active antiretroviral therapy.
Apoptosis has been proposed as a mechanism responsible for T cell depletion in HIV-1 infection. In the present study we have phenotyped apoptotic T cells in tonsillar lymphoid tissue from 11 HIV-1-infected patients by flow cytometry light-scatter characteristics during 48 weeks of highly active antiretroviral therapy (HAART). We found that the decline in tonsillar viral load was associated with a decrease in the proportion of apoptotic CD4+ and CD8+ T cells. CD4 cell apoptosis was predominantly seen within the memory CD28+ Fas+ FasL+ population. The increased level of apoptotic CD8+ T cells was found among activated Fas+ memory cells irrespective of CD28 and FasL expression. These T cell subsets were expanded in untreated infection, but normalized with therapy. We conclude that HIV-1 triggers FasL-mediated apoptosis of uninfected CD4+ T cells, whereas CD8+ T cell apoptosis is driven by chronic immune activation. Virus suppression reverses both of these mechanisms, contributing to immune reconstitution during HAART.
Dyrhol-Riise
A M
AM
Centre for Research in Virology, Department of Microbiology and Immunology, P.O. Box 7800, University of Bergen, N-5020 Bergen, Norway. annema.riise@vir.uib.no
Stent
G
G
Røsok
B I
BI
Voltersvik
P
P
Olofsson
J
J
Asjö
B
B
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000276:immunology; D023241:Antiretroviral Therapy, Highly Active; D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology*; D053222:Fas Ligand Protein; D015497:HIV-1; D006801:Humans; D008221:Lymphoid Tissue / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000032:analysis*; D011446:Prospective Studies; D019014:fas Receptor / Q000032:analysis*
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D019014:fas Receptor