Persistent and Selective Deficiency of CD4+ T Cell Immunity to Cytomegalovirus in Immunocompetent Young Children

• Published in: The Journal of immunology (1950) Vol. 172; no. 5; pp. 3260 - 3267
• Main Authors: Tu, Wenwei, Chen, Sharon, Sharp, Margaret, Dekker, Corry, Manganello, Anne Marie, Tongson, Eileen C, Maecker, Holden T, Holmes, Tyson H, Wang, Zhaoti, Kemble, George, Adler, Stuart, Arvin, Ann, Lewis, David B
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 01-03-2004
• Subjects: Adult; Age Factors; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; CD4-Positive T-Lymphocytes - virology; CD40 Ligand - biosynthesis; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - virology; Child, Preschool; Cytomegalovirus - immunology; Cytomegalovirus Infections - immunology; Cytomegalovirus Infections - virology; Female; Humans; Immunity, Cellular; Immunologic Memory; Infant; Interferon-gamma - biosynthesis; Interleukin-2 - antagonists & inhibitors; Interleukin-2 - biosynthesis; Lymphocyte Count; Male; Middle Aged; Receptors, CCR7; Receptors, Chemokine - biosynthesis; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; T-Lymphocyte Subsets - virology; Th1 Cells - immunology; Th1 Cells - metabolism; Th1 Cells - virology; Virus Shedding - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.172.5.3260

Healthy young children who acquire CMV have prolonged viral shedding into the urine and saliva, but whether this is attributable to limitations in viral-specific immune responses has not been explored. In this study, we found that otherwise immunocompetent young children after recent primary CMV infection accumulated markedly fewer CMV-specific CD4(+) T cells that produced IFN-gamma than did adults. These differences in CD4(+) T cell function persisted for more than 1 year after viral acquisition, and did not apply to CMV-specific IFN-gamma production by CD8(+) T cells. The IFN-gamma-producing CD4(+) T cells of children or adults that were reactive with CMV Ags were mainly the CCR7(low) cell subset of memory (CD45R0(high)CD45RA(low)) cells. The decreased IFN-gamma response to CMV in children was selective, because their CCR7(low) memory CD4(+) T cells and those of adults produced similar levels of this cytokine after stimulation with staphylococcal enterotoxin B superantigen. CD4(+) T cells from children also had reduced CMV-specific IL-2 and CD154 (CD40 ligand) expression, suggesting an early blockade in the differentiation of viral-specific CD4(+) T cells. Following CMV acquisition, children, but not adults, persistently shed virus in urine, and this was observable for at least 29 mo postinfection. Thus, CD4(+) T cell-mediated immunity to CMV in humans is generated in an age-dependent manner, and may have a substantial role in controlling renal viral replication and urinary shedding.