Selective depletion of high-avidity human immunodeficiency virus type 1 (HIV-1)-specific CD8+ T cells after early HIV-1 infection.
Human immunodeficiency virus type 1 (HIV-1)-specific CD8+ T cells in early infection are associated with the dramatic decline of peak viremia, whereas their antiviral activity in chronic infection is less apparent. The functional properties accounting for the antiviral activity of HIV-1-specific CD8+ T cells during early infection are unclear. Using cytokine secretion and tetramer decay assays, we demonstrated in intraindividual comparisons that the functional avidity of HIV-1-specific CD8+ T cells was consistently higher in early infection than in chronic infection in the presence of high-level viral replication. This change of HIV-1-specific CD8+ T-cell avidity between early and chronic infections was linked to a substantial switch in the clonotypic composition of epitope-specific CD8+ T cells, resulting from the preferential loss of high-avidity CD8+ T-cell clones. In contrast, the maintenance of the initially recruited clonotypic pattern of HIV-1-specific CD8+ T cells was associated with low-level set point HIV-1 viremia. These data suggest that high-avidity HIV-1-specific CD8+ T-cell clones are recruited during early infection but are subsequently lost in the presence of persistent high-level viral replication.
Lichterfeld
Mathias
M
Partners AIDS Research Center, Massachusetts General Hospital, and Division of AIDS, Harvard Medical School, Boston, MA 02129, USA.
Yu
Xu G
XG
Mui
Stanley K
SK
Williams
Katie L
KL
Trocha
Alicja
A
Brockman
Mark A
MA
Allgaier
Rachel L
RL
Waring
Michael T
MT
Koibuchi
Tomohiko
T
Johnston
Mary N
MN
Cohen
Daniel
D
Allen
Todd M
TM
Rosenberg
Eric S
ES
Walker
Bruce D
BD
Altfeld
Marcus
M
D000328:Adult; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D015550:Cell Degranulation; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D005434:Flow Cytometry; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology* / Q000502:physiology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014766:Viremia
D016207:Cytokines; D011948:Receptors, Antigen, T-Cell