A shift to Th0 cytokine production by CD4⁺ cells in human longevity: Studies on two healthy centenarians

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-γ and IL-4) and compared them with TCC obtained by three young normal subjects; in all 180 TCC were analyzed. In young donors, 35 TCC were CD4⁺, 56 CD8⁺ and 2 were αβCD4^-CD8^- (double negative). In centenarians, we obtained 46 CD4⁺ TCC, 38 CD8⁺, 2 CD4⁺CD8⁺ (double positive) and 1 γδ⁺ double negative. Of the young subjects' TCC, 71% produced IFN-γ 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 93 TCC and 2 out of 87 TCC, respectively). The intermediate profile of TCC producing both IL-4 and IFN-γ (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.