Distinct kinetics of Gag-specific CD4+ and CD8+ T cell responses during acute HIV-1 infection

• Published in: The Journal of immunology (1950) Vol. 188; no. 5; pp. 2198 - 2206
• Main Authors: Riou, Catherine, Ganusov, Vitaly V, Campion, Suzanne, Mlotshwa, Mandla, Liu, Michael K P, Whale, Victoria E, Goonetilleke, Nilu, Borrow, Persephone, Ferrari, Guido, Betts, Michael R, Haynes, Barton F, McMichael, Andrew J, Gray, Clive M
• Format: Journal Article
• Language: English
• Published: United States 01-03-2012
• Subjects: Acute Disease; Adolescent; Adult; Amino Acid Sequence; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - pathology; CD4-Positive T-Lymphocytes - virology; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - pathology; CD8-Positive T-Lymphocytes - virology; Cells, Cultured; Chronic Disease; Cohort Studies; Female; gag Gene Products, Human Immunodeficiency Virus - immunology; HIV Infections - immunology; HIV Infections - pathology; Human immunodeficiency virus 1; Humans; Lymphocyte Activation - immunology; Male; Molecular Sequence Data; Time Factors; Young Adult
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1102813

HIV infection is characterized by a gradual deterioration of immune function, mainly in the CD4 compartment. To better understand the dynamics of HIV-specific T cells, we analyzed the kinetics and polyfunctional profiles of Gag-specific CD4(+) and CD8(+) T cell responses in 12 subtype C-infected individuals with different disease-progression profiles, ranging from acute to chronic HIV infection. The frequencies of Gag-responsive CD4(+) and CD8(+) T cells showed distinct temporal kinetics. The peak frequency of Gag-responsive IFN-γ(+)CD4(+) T cells was observed at a median of 28 d (interquartile range: 21-81 d) post-Fiebig I/II staging, whereas Gag-specific IFN-γ(+)CD8(+) T cell responses peaked at a median of 253 d (interquartile range: 136-401 d) and showed a significant biphasic expansion. The proportion of TNF-α-expressing cells within the IFN-γ(+)CD4(+) T cell population increased (p = 0.001) over time, whereas TNF-α-expressing cells within IFN-γ(+)CD8(+) T cells declined (p = 0.005). Both Gag-responsive CD4(+) and CD8(+) T cells showed decreased Ki67 expression within the first 120 d post-Fiebig I/II staging. Prior to the disappearance of Gag-responsive Ki67(+)CD4(+) T cells, these cells positively correlated (p = 0.00038) with viremia, indicating that early Gag-responsive CD4 events are shaped by viral burden. No such associations were observed in the Gag-specific CD8(+) T cell compartment. Overall, these observations indicated that circulating Gag-responsive CD4(+) and CD8(+) T cell frequencies and functions are not synchronous, and properties change rapidly at different tempos during early HIV infection.