Direct measurement of CD4+ and CD8+ T-cell responses to CMV in HIV-1-infected subjects.
Data from murine models of chronic viral infection suggest that CD4+ T-cell responses to viral pathogens are important in sustaining the number and/or function of CD8+ cytotoxic T-cell (CTL) effectors. In this study, we used cytokine flow cytometry (CFC), staining with HLA-A*0201-peptide tetramers, and peptide stimulation with epitopic peptides to study functional CD4+ and CD8+ T-cell responses to cytomegalovirus (CMV) in human subjects coinfected with CMV and the human immunodeficiency virus, type 1 (HIV-1). We show that strong CD4+ and CD8+ T-cell responses to CMV antigens are sustained over time in HIV-1-infected individuals. Those who maintain a strong CD4+ T-cell response to CMV are also likely to maintain higher frequencies of CD8+ T cells capable of binding to HLA-A*0201-CMV pp65 (A2-pp65) tetramers as well as responses to pp65 peptide stimulation with effector cytokine production. These data support the hypothesis that declines in frequencies of CD4+ T-cell responses to CMV are associated with an inability to sustain high levels of CMV-specific CD8+ T-cell responses in HIV-1-infected subjects. These declines may precede the onset of CMV-associated end organ disease.
Komanduri
K V
KV
Gladstone Institute of Virology and Immunology, San Francisco, California 94141-9100, USA.
Donahoe
S M
SM
Moretto
W J
WJ
Schmidt
D K
DK
Gillespie
G
G
Ogg
G S
GS
Roederer
M
M
Nixon
D F
DF
McCune
J M
JM
D000914:Antibodies, Viral / Q000097:blood; D000956:Antigens, Viral / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002908:Chronic Disease; D003587:Cytomegalovirus / Q000276:immunology; D003586:Cytomegalovirus Infections / Q000150:complications / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D015658:HIV Infections / Q000150:complications / Q000276:immunology* / Q000821:virology; D015497:HIV-1; D015234:HLA-A Antigens / Q000032:analysis; D006801:Humans; D018655:Lymphocyte Count; D008297:Male; D010750:Phosphoproteins / Q000494:pharmacology; D011446:Prospective Studies; D014763:Viral Matrix Proteins / Q000494:pharmacology
D000914:Antibodies, Viral; D000956:Antigens, Viral; D015234:HLA-A Antigens; D010750:Phosphoproteins; D014763:Viral Matrix Proteins; C065418:cytomegalovirus matrix protein 65kDa