Longevity in vitro of human CD4+ T helper cell clonesderived from young donors and elderly donors, or fromprogenitor cells: age-associated differences in cellsurface molecule expression and cytokine secretion
Tóm tắt
The effectiveness of the adaptive immune system reliesupon extensive proliferation of an initially smallnumber of antigen-specific T cells. At the end of asuccessful response, the majority die by apoptosis anda small minority joins the memory cell pool. Uponre-challenge with antigen, these memory cells mustagain undergo clonal expansion in order to mediate aneffective response. Thus, T cells are subjected tomarked proliferative stress which may result in clonalexhaustion due to replicative senescence. In othersystems made up of rapidly proliferating cells (e.g. inthe gut) individual clones are identical and arereplaced at the end of their lifespan bydifferentiation from a stem cell reservoir. However,because of the unique clonal distribution of antigenreceptors on T cells, mere replacement with other Tcells is not sufficient to maintain the integrity ofthe system. Moreover, the very source of new T cellsdecreases with age (due to thymic involution).Therefore, the adaptive immune system may be uniquelysusceptible to the deleterious effects of replicativesenescence. Particularly in humans, in vivo studies ofthe behaviour of individual T-cell clones in the bodyis difficult. However, T-cell longevity, measured asproliferative capacity in terms of populationdoublings, can be usefully modelled at the clonallevel in vitro. This paper discusses the surprisinglylittle that is known about the average longevity,variation between clones, and the maximal longevity ofhuman T cells under clonal culture conditions invitro. From our own studies, we show that averagelifespan of human T cells is as little as 17 PD;however, established clones reach 35 PD on average,with maximum longevity generally in the region of 60–80 PD, regardless of the source of the cloned cells.Expression of surface molecules in general did notdiffer strikingly between young and old donors, butthe frequency of clones secreting IL-10, and theamount secreted per clone was higher in the elderlythan in the young. Conversely, the frequency of clonessecreting IL-6 and the amount secreted per clone washigher in the young.
Tài liệu tham khảo
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