Infrequent detection of HIV-1-specific, but not cytomegalovirus-specific, CD8(+) T cell responses in young HIV-1-infected infants
Graduate Program in Immunology/Virology; Department of Pediatrics; Program in Molecular Medicine
AIDS-Related Opportunistic Infections; Antigen-Presenting Cells; Antigens, Viral; CD8-Positive T-Lymphocytes; Cell Line, Transformed; Cells, Cultured; Cytomegalovirus; Cytomegalovirus Infections; Enzyme-Linked Immunosorbent Assay; HIV Antigens; HIV Infections; HIV-1; Humans; Infant; Interferon Type II; Kinetics; Lymphocyte Activation; Lymphocyte Depletion; Virus Replication
Life Sciences | Medicine and Health Sciences
Early potent combination antiretroviral therapies (ART) for HIV-1 infection can preserve or restore immune function, but control of viral replication early in infection may interfere with the development of HIV-1-specific immune responses. Using an IFN-gamma ELISPOT assay, we evaluated the breadth and intensity of HIV-1-specific CD8(+) T cell responses in 17 vertically infected infants who began ART at 1-23 mo of age. CMV-specific responses were also characterized in three infants coinfected with HIV-1 and CMV. Before ART, HIV-1-specific CD8(+) T cell responses were detected in two of 13 (15%) infantsCD8(+) T cells became undetectable in these two infants after the control of viral replication. Intermittent HIV-1-specific responses were noted in six infants who did not experience durable control of viral replication. In contrast, HIV-1-specific responses were detected before ART in four of four infants >6 mo of age and became persistently undetectable in only one child. CMV-specific CD8(+) T cell responses were persistently detected in all HIV-1 and CMV coinfected infants. In conclusion, HIV-1-specific CD8(+) T cell responses were less commonly detected before therapy in young infants than in older infants. Suppression of viral replication appeared to interfere with the development and maintenance of HIV-1-specific CD8(+) T cell responses. The detection of CMV-specific responses in HIV-1 and CMV coinfected infants suggests a selective defect in the generation or maintenance of HIV-1-specific CD8(+) T cell responses. Therapeutic HIV-1 vaccine strategies in young infants may prolong the clinical benefit of ART by expanding the HIV-1-specific CD8(+) T cell pool.
DOI of Published Version
J Immunol. 2001 Dec 15;167(12):7134-40.
Journal of immunology (Baltimore, Md. : 1950)
Scott, Zachary Aaron; Chadwick, Ellen G.; Gibson, Laura L.; Catalina, Michelle D.; McManus, Margaret M.; Yogev, Ram; Palumbo, Paul; Sullivan, John L.; Britto, Paula; Gay, Hannah; and Luzuriaga, Katherine, "Infrequent detection of HIV-1-specific, but not cytomegalovirus-specific, CD8(+) T cell responses in young HIV-1-infected infants" (2001). Open Access Articles. 1123.