Low levels of perforin expression in CD8+ T lymphocyte granules in lymphoid tissue during acute human immunodeficiency virus type 1 infection.
Human immunodeficiency virus (HIV)-specific cytotoxic T lymphocyte (CTL) responses are detectable shortly after the acute phase of HIV infection, but they cannot control viral replication and prevent development of chronic immune suppression. This article describes a defect in the coexpression of perforin in granzyme A-positive CD8(+) T cells in lymphoid tissue from patients with acute HIV infection and a reduction in the perforin-dependent nuclear translocation of granzyme A. Furthermore, intracellular levels of HIV DNA and RNA found in lymphoid tissue were higher (10-100 times) than those found in blood, and blood samples showed more-coordinated cellular perforin/granzyme A expression. This suggests that mechanisms inhibiting CTL-mediated cytotoxicity are operative in lymphoid tissue early in the course of HIV infection.
Andersson
Jan
J
Department of Medicine, Center for Infectious Medicine, Karolinska Institutet, Huddinge University Hospital, Stockholm, Sweden. Jan.Andersson@medhs.ki.se
Kinloch
Sabine
S
Sönnerborg
Anders
A
Nilsson
Jakob
J
Fehniger
Thomas E
TE
Spetz
Anna-Lena
AL
Behbahani
Homira
H
Goh
Li-Ean
LE
McDade
Hugh
H
Gazzard
Brian
B
Stellbrink
Hans
H
Cooper
David
D
Perrin
Luc
L
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000821:virology; D000208:Acute Disease; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D004279:DNA, Viral / Q000097:blood; D053804:Granzymes; D015497:HIV-1; D006801:Humans; D008221:Lymphoid Tissue / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D012333:RNA, Messenger / Q000032:analysis; D012367:RNA, Viral / Q000097:blood; D012697:Serine Endopeptidases / Q000097:blood; D019562:Viral Load
D004279:DNA, Viral; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D012333:RNA, Messenger; D012367:RNA, Viral; D054353:Perforin; D053804:Granzymes; D012697:Serine Endopeptidases; C509212:GZMA protein, human