Phenotypic and functional characterization of HIV-1-specific CD4+CD8+ double-positive T cells in early and chronic HIV-1 infection.
OBJECTIVE
CD4+CD8+ double-positive (DP) T cells represent a poorly characterized population of effector T cells found at low frequencies in the peripheral blood. Virus-specific DP T cells have been identified in HIV-1-infected patients but their origin, relationship to conventional CD4+ and CD8+ single-positive (SP) T cells, and role in disease pathogenesis are unclear.


METHODS
In this study, peripheral blood T cells were analyzed for cytokine production, maturation, and cytolytic marker expression by polychromatic flow cytometry in subjects with both early (n = 27) and chronic (n = 21) HIV-1 infection.


CONCLUSIONS
HIV-1-specific interferon gamma (IFN-g)-producing DP T cells were identified at a median frequency of 0.48% compared with 1.08% and 0.02% for CD8 and CD4 SP cells, respectively, in response to pooled HIV-1 peptides. HIV-1- specific DP T cells exhibited polyfunctionality with characteristics of both CD4 and CD8 SP T cells, including coproduction of IFN-gamma and IL-2 and expression of cytolytic-associated lysosomal-associated membrane protein. No differences in frequencies of unstimulated DP T cells were observed in early compared with chronic infection. However, chronic infection was associated with higher frequencies of HIV-specific, IFN-gamma-producing DP T cells and higher fractions of effector memory and lysosomal-associated membrane protein expression among these cells, suggesting an effect of cumulative viral antigen burden on DP T-cell function.
Howe
Rawleigh
R
University of Colorado Denver, Aurora, CO, USA.
Dillon
Stephanie
S
Rogers
Lisa
L
Palmer
Brent
B
MaWhinney
Samantha
S
Blyveis
Naomi
N
Schlichtemeier
Rick
R
D'Souza
Michelle
M
Ingoldby
Laura
L
Harwood
Jeri E F
JE
Rietmeijer
Cornelis
C
Ray
Graham
G
Connick
Elizabeth
E
Wilson
Cara C
CC
D000328:Adult; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology*; D002908:Chronic Disease; D016207:Cytokines / Q000378:metabolism; D005260:Female; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1; D006801:Humans; D007156:Immunologic Memory; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D019562:Viral Load; D055815:Young Adult
D016207:Cytokines