CD45 ISOFORMS EXPRESSION ON CD4(-CELLS THROUGHOUT LIFE, FROM NEWBORNSTO CENTENARIANS - IMPLICATIONS FOR T-CELL MEMORY() AND CD8(+) T)

CD4(+) and CD8(+) peripheral blood T lymphocytes show mutually exclusi ve expression of CD45RA or CD45R0, two isoforms of the common leukocyt e antigen that seem to recognize so-called virgin/unprimed and memory/ activated T cells. The expression of these isoforms has been studied b y three colour cytofluorimetric analysis on CD4(+) or CD8(+) periphera l blood CD3(+) cells from 22 healthy centenarians, analyzed in a conte xt of 202 healthy donors 0-110 years old. An age-related unbalance of virgin and memory cells was found between CD4(+) and CD8(+) subsets. A s expected, at birth 95-99% of the CD3(+) lymphocytes expressed the CD 45RA isoform. A rapid increase of CD45R0(+) cells was observed in the first 2-3 decades of life, this phenomenon being much more pronounced on CD4(+) cells. Subsequently, the increase of the 'memory' compartmen t was much less rapid, so that in centenarians a consistent reservoire of CD45RA(+) among CD4(+) cells was still present (about 20%). In the se exceptional individuals the percentage of CD45RA(+) cells among CD8 (+) T lymphocytes was even higher (about 50%), and only slightly lower than that of young donors (about 55-60%). Thus, the main changes occu rred at a different rate in CD4(+) (about 20%). In these exceptional i ndividuals the percentage of CD45RA(+) cells among CD8(+) T lymphocyte s was even higher (about 50%), and only slightly lower than that of yo ung donors (about 55-60%). Thus, the main changes occurred at a differ ent rate in CD4(+) and in CD8(+) T cells, at an age of between 0 and 3 0 years, when the thymus is still functionally active. Interestingly, no difference in the usage of CD45 isoforms was observed within T cell s bearing four different VP-T cell receptor (TCR). The significance of this age-related unbalance is unknown. However, the presence of a gre at number of CD45RA(+) T lymphocytes within the CD4(+) and the CD8(+) T cell subsets even in the peripheral blood of centenarians poses the problem of their origin (thymus? extrathymic sites?), of their functio nal role and of their lifespan. Moreover, the data on centenarians sug gest that they may represent a very selected population where a slowin g of immunosenescence occurs.