Fully differentiated HIV-1 specific CD8+ T effector cells are more frequently detectable in controlled than in progressive HIV-1 infection.
BACKGROUND
CD8+ T cells impact control of viral infections by direct elimination of infected cells and secretion of a number of soluble factors. In HIV-1 infection, persistent HIV-1 specific IFN-gamma+ CD8+ T cell responses are detected in the setting of disease progression, consistent with functional impairment in vivo. Recent data suggest that impaired maturation, as defined by the lineage markers CD45RA and CCR7, may contribute to a lack of immune control by these responses.


RESULTS
We investigated the maturation phenotype of epitope-specific CD8+ T cell responses directed against HIV-1 in 42 chronically infected, untreated individuals, 22 of whom were "Controllers" (median 1140 RNA copies/ml plasma, range<50 to 2520), and 20 "progressors" of whom had advanced disease and high viral loads (median 135,500 RNA copies/ml plasma, range 12100 to >750000). Evaluation of a mean of 5 epitopes per person revealed that terminally differentiated CD8+ T cells directed against HIV-1 are more often seen in HIV-1 Controllers (16/22; 73%) compared to HIV-1 progressors (7/20; 35%)(p = 0.015), but the maturation state of epitope-specific responses within a given individual was quite variable. Maturation phenotype was independent of the HLA restriction or the specificity of a given CD8+ T cell response and individual epitopes associated with slow disease progression were not more likely to be terminally differentiated.


CONCLUSIONS
These data indicate that although full maturation of epitope-specific CD8+ T cell responses is associated with viral control, the maturation status of HIV-1 specific CD8+ T cell responses within a given individual are quite heterogeneous, suggesting epitope-specific influences on CD8+ T cell function.
Addo
Marylyn M
MM
Partners AIDS Research Center and Infectious Disease Division, Massachusetts General Hospital and Harvard Medical School Division of AIDS, Boston, Massachusetts, United States of America.
Draenert
Rika
R
Rathod
Almas
A
Verrill
Cori L
CL
Davis
Benjamin T
BT
Gandhi
Rajesh T
RT
Robbins
Gregory K
GK
Basgoz
Nesli O
NO
Stone
David R
DR
Cohen
Daniel E
DE
Johnston
Mary N
MN
Flynn
Theresa
T
Wurcel
Alysse G
AG
Rosenberg
Eric S
ES
Altfeld
Marcus
M
Walker
Bruce D
BD
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000473:pathology; D000293:Adolescent; D001900:Boston; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology / Q000821:virology*; D002454:Cell Differentiation; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D000939:Epitopes / Q000032:analysis; D015658:HIV Infections / Q000276:immunology* / Q000473:pathology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007700:Kinetics; D012367:RNA, Viral / Q000097:blood; D013601:T-Lymphocytes / Q000276:immunology / Q000821:virology; D019562:Viral Load; D014766:Viremia / Q000188:drug therapy; D055815:Young Adult
D000939:Epitopes; D012367:RNA, Viral