title: Evidence of premature immune aging in patients thymectomized during early childhood.
abstract: While the thymus is known to be essential for the initial production of T cells during early life, its contribution to immune development remains a matter of debate. In fact, during cardiac surgery in newborns, the thymus is completely resected to enable better access to the heart to correct congenital heart defects, suggesting that it may be dispensable during childhood and adulthood. Here, we show that young adults thymectomized during early childhood exhibit an altered T cell compartment. Specifically, absolute CD4+ and CD8+ T cell counts were decreased, and these T cell populations showed substantial loss of naive cells and accumulation of oligoclonal memory cells. A subgroup of these young patients (22 years old) exhibited a particularly altered T cell profile that is usually seen in elderly individuals (more than 75 years old). This condition was directly related to CMV infection and the induction of strong CMV-specific T cell responses, which may exhaust the naive T cell pool in the absence of adequate T cell renewal from the thymus. Together, these marked immunological alterations are reminiscent of the immune risk phenotype, which is defined by a cluster of immune markers predictive of increased mortality in the elderly. Overall, our data highlight the importance of the thymus in maintaining the integrity of T cell immunity during adult life.
authors.affiliation: Infections and Immunity, INSERM UMRS 945, Avenir Group, Hôpital Pitié-Salpêtrière, UPMC University of Paris 06, Paris, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Sauce
authors.forename: Martin
authors.initials: M
authors.lastname: Larsen
authors.forename: Solène
authors.initials: S
authors.lastname: Fastenackels
authors.forename: Anne
authors.initials: A
authors.lastname: Duperrier
authors.forename: Michael
authors.initials: M
authors.lastname: Keller
authors.forename: Beatrix
authors.initials: B
authors.lastname: Grubeck-Loebenstein
authors.forename: Christophe
authors.initials: C
authors.lastname: Ferrand
authors.forename: Patrice
authors.initials: P
authors.lastname: Debré
authors.forename: Daniel
authors.initials: D
authors.lastname: Sidi
authors.forename: Victor
authors.initials: V
authors.lastname: Appay
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002675:Child, Preschool; D016207:Cytokines / Q000276:immunology; D003586:Cytomegalovirus Infections / Q000276:immunology; D006801:Humans; D007107:Immune System / Q000276:immunology*; D007231:Infant, Newborn / Q000276:immunology; D008875:Middle Aged; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013934:Thymectomy / Q000009:adverse effects*; D055815:Young Adult
chemical_list: D016207:Cytokines