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Minerva Biotecnologica 1998 June;10(2):77-80

language: English

Immune func­tion in extreme­ly old ­humans

Sansoni P.

Department of General Medicine and Therapy, University of Parma, Italy


It is gen­er­al­ly ­believed ­that the ­immune func­tion pro­gres­sive­ly dete­ri­orates ­with age. However, by select­ing ­healthy sub­jects by a ­strict pro­to­col (­SENIEUR), sev­er­al ­immune ­defects ­were not detect­able ­with age. In ­this ­regard, the ­study of sev­er­al ­immune param­e­ters ­revealed sig­nif­i­cant chang­es in the T ­cell sub­sets accom­pa­nied by an ­increase of ­cells ­with NK mark­ers and a sig­nif­i­cant ­decrease of B ­cells. At the func­tion­al lev­el, nat­u­ral kill­er and ­anti-CD16 redi­rect­ed kill­ing activ­ities of extreme­ly old sub­jects ­were com­par­able to ­those of ­young con­trols, ­while mid­dle-­aged sub­jects ­showed, sur­pris­ing­ly, a sig­nif­i­cant reduc­tion of ­unknown ori­gin. An impor­tant and exten­sive­ly stud­ied ­immune func­tion is lym­pho­cyte capa­bil­ity to pro­life­rate. By ­using sev­er­al mito­gens includ­ing mem­brane and trans­mem­brane stim­u­li a “com­plex pat­tern” of lym­pho­cyte pro­life­ra­tive capa­bil­ity emerg­es. In par­tic­u­lar, by ­using ­some stim­u­li (PHA, rIL2 or MLRs) a pro­gres­sive age-depen­dent ­decline in the lym­pho­cyte pro­life­ra­tive ­response ­occurs. However, by ­using ­more clear­ly ­defined stim­u­li (­anti-CD3 mAb or PMA) no dif­fer­enc­es in the pro­life­ra­tive capa­bil­ity ­between cent­en­ar­ians, mid­dle-­aged and ­young sub­jects are ­observed. Furthermore, the ­study of the ­main cos­ti­mu­la­to­ry path­way, via CD28 mole­cule, func­tion ­well dur­ing the ­aging pro­cess includ­ing cent­en­ar­ians. Thus, sev­er­al impor­tant acti­va­tion path­ways are ­well pre­served ­with age. Regarding humo­ral immu­nity, it was ­observed ­that ­organ-spe­cif­ic auto­-an­ti­bod­ies (­anti-Thyroglobulin, ­anti-per­ox­i­dase) pro­gres­sive­ly ­increase ­with age but are vir­tu­al­ly ­absent in cent­en­ar­ians. However, it has sub­se­quent­ly ­been ­shown ­that ­organ-spe­cif­ic ­auto-anti­bod­ies ­were ­also ­absent in ­healthy old sub­jects. Moreover, ser­um IgG and IgA ­were sig­nif­i­cant­ly ­raised ­with age ­while IgM ­remained ­unchanged. In con­trast ­with the ­increase of Ig, we ­observed a pro­gres­sive reduc­tion of cir­cu­lat­ing B ­cells includ­ing B ­cells express­ing CD5 mole­cule (a sub­set ­able to ­secrete ­poly-reac­tive ­auto-anti­bod­ies). In con­clu­sion, care­ful stud­ies of ­healthy ­humans ­from new­borns to cent­en­ar­ians sug­gest ­that a con­tin­u­ous “remod­el­ing” ­occurs ­with age. Indeed, the ­aging pro­cess is not asso­ciat­ed, as pre­vi­ous­ly ­thought, ­with a pro­gres­sive dete­ri­ora­tion of the ­immune func­tion, but ­some impor­tant ­immune param­e­ters are ­well pre­served ­until the ­last ­decades of ­human ­life like­ly con­trib­ute to reach­ing ­this ­advanced age.

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