CD95-induced apoptosis contributes to loss of primed/memory but not resting/naive T cells in children infected with human immunodeficiency virus type 1.
Increased apoptosis of uninfected CD4+ T cells is involved in CD4+ T cell depletion in HIV-1+ individuals. Recently, a progressive loss of resting naive T cells has been shown during the asymptomatic stage of HIV infection in children and adults. The CD95 receptor/ligand system is a key regulator of T cell apoptosis. To elucidate the role of this system in the depletion of resting naive T cells, we studied expression of CD95 and sensitivity toward CD95-triggered apoptosis in T cell subsets defined by CD45 (leukocyte common antigen) isoforms and CD62L (lymphocyte homing receptor L-selectin) in a cohort of HIV-1+ children. In patients and healthy control subjects the level of CD95 expression increased from resting/naive (L-selectin(bright) CD45RA+) T cells to primed/memory (CD45RO+ CD45RA-) T cells. In HIV-1+ children the susceptibility of peripheral blood T cells for CD95-mediated apoptosis also increased with progressive differentiation toward primed/memory T cells. Resting/ naive T cells were resistant to spontaneous and anti-CD95-induced apoptosis. Loss of naive (CD45RA+ CD45RO-) T cells in HIV-1+ patients in vivo was found to be paralleled by an increase in the percentage of CD95high T cells as well as an increase in anti-CD95-induced apoptosis of CD4+ and CD8+ T cells. We conclude that loss of naive unprimed T cells during the asymptomatic phase of HIV-1 infection is caused by continuous generation of primed cells that exhibit increased sensitivity toward CD95-mediated apoptotic cell death in vitro.
Böhler
T
T
University Children's Hospital, Heidelberg, Germany.
Nedel
S
S
Debatin
K M
KM
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology*; D000293:Adolescent; D000328:Adult; D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D005260:Female; D015497:HIV-1; D006801:Humans; D007156:Immunologic Memory; D016130:Immunophenotyping; D007223:Infant; D017493:Leukocyte Common Antigens / Q000032:analysis; D008297:Male; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D012016:Reference Values; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000473:pathology; D019014:fas Receptor / Q000096:biosynthesis / Q000502:physiology*
D019014:fas Receptor; D017493:Leukocyte Common Antigens; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1