title: A shift to Th0 cytokine production by CD4+ cells in human longevity: studies on two healthy centenarians.
abstract: Centenarians, particularly healthy centenarians, constitute the example of successful aging and the study of their immune status can help to define the endpoint of the changes occurring throughout life. We characterized T cell clones (TCC) of two healthy centenarians, studying their phenotypes and production of representative Th1 and Th2 cytokines (IFN-gamma and IL-4) and compared them with TCC obtained by three young normal subjects; in all 180TCC were analyzed. In young donors, 35TCC were CD4+, 56CD8+ and 2 were alpha beta +CD4-CD8- (double negative). In centenarians, we obtained 46CD4+TCC, 38CD8+, 2CD4+CD8+ (double positive) and 1 gamma delta + double negative. Of the young subjects' TCC, 71% produced IFN-gamma but no IL-4 (Th1 pattern) and this prevalence decreased to 39% in TCC from the centenarians. The number of clones showing the opposite Th2 pattern was similar in young and aged donors (3 out of 93TCC and 2 out of 87TCC, respectively). The intermediate profile of TCC producing both IL-4 and IFN-gamma (Th0) was found in 25.8% of clones from young people, but it almost doubled to 58.6% in centenarians. The analysis shows that the Th profiles of CD8+TCC is nearly superimposable in the two groups, whereas a major shift from a Th1 to a Th0 pattern is presented by CD4+TCC. The balance provided by a majority of CD4+TCC showing a Th0 pattern may ensure both humoral and cell-mediated defences. In CD8+TCC, however, a Th1 pattern still is present, possibly for efficient generation of cytotoxic responses. These findings should be extended by studying other centenarians and elderly subjects.
authors.affiliation: Department of Clinical Medicine, University La Sapienza, Rome, Italy. paganelli@axrma.uniroma1.it
authors.forename: R
authors.initials: R
authors.lastname: Paganelli
authors.forename: E
authors.initials: E
authors.lastname: Scala
authors.forename: R
authors.initials: R
authors.lastname: Rosso
authors.forename: A
authors.initials: A
authors.lastname: Cossarizza
authors.forename: L
authors.initials: L
authors.lastname: Bertollo
authors.forename: D
authors.initials: D
authors.lastname: Barbieri
authors.forename: A
authors.initials: A
authors.lastname: Fabrizi
authors.forename: E A
authors.initials: EA
authors.lastname: Lusi
authors.forename: U
authors.initials: U
authors.lastname: Fagiolo
authors.forename: C
authors.initials: C
authors.lastname: Franceschi
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002999:Clone Cells; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000096:biosynthesis*; D008136:Longevity / Q000276:immunology*; D008297:Male
chemical_list: D015847:Interleukin-4; D007371:Interferon-gamma