Young Infants Lack HIV-Specific CD8+ T Cell Response
Originally published by Reuters Health, January 4, 2002
NEW YORK (Reuters Health) — Infants younger than 6 months commonly lack a CD8+ T cell response to vertically transmitted HIV infection, according to a report in the December 15 issue of the Journal of Immunology.
HIV-1-specific CD8+ T cell responses play an important role in the control of HIV-1 replication during the acute and chronic phases of the infection, the authors explain, and previous work has shown that infants treated early with antiretroviral therapy lack persistent responses.
Dr. Katherine Luzuriaga, from University of Massachusetts Medical School in Worcester, and colleagues serially evaluated HIV-specific CD8+ T cell responses in 17 vertically infected infants who received antiretroviral therapy beginning at 1 to 23 months of age.
All 4 infants over 6 months of age produced CD8+ T cell interferon (IFN)-gamma responses to at least one HIV-1 gene product prior to antiretroviral therapy, the authors report, whereas only two of 13 infants younger than 6 months produced such responses.
Once antiretroviral therapy began, CD8+ T cell responses of both of the younger infants became undetectable, the report indicates. All four of the older infants, however, continued to produce IFN-gamma responses, and in three of them, CD8+ T cell responses were detected even after control of viral replication.
In contrast, CMV-specific CD8+ T-cell responses were detected in all three young infants coinfected with CMV after initiation of antiretroviral therapy, suggesting "that the paucity of detectable HIV-1-specific CD8+ T cell responses represents a selective defect in the generation or maintenance of HIV-1-specific CD8+ T cells," the researchers note.
"These data demonstrate the decreased frequency of detection and magnitude of early HIV-1 specific CD8+ T cell responses in young (< 6 months of age) vertically infected infants," Dr. Luzuriaga told Reuters Health, "which might help to explain the persistently high levels of plasma viremia observed in early vertical infection. Early control of viral replication through early therapy may further limit the development of HIV-specific CD8+ T cell responses."
"Two main strategies have been proposed to boost HIV-1 specific CD8+ T cell responses in adults and children treated during primary infection: HIV-specific vaccination and structured interruption of antiretroviral therapy," Dr. Luzuriaga continued. "We would be reluctant to interrupt therapy and have proposed immunization of these infants with an HIV-specific vaccine. A phase I trial of the safety and immunogenicity of an MVA/fowlpox vaccine regimen in these infants is planned for spring 2002."
