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Thymic function in young/old chimeras: substantial thymic T cell regenerative capacity despite irreversible age-associated thymic involution.

Abstract：

:Age-associated thymic involution results in a diminished capacity to regenerate T cell populations, although the magnitude of this effect is unknown. In this report, thymic function was studied in aged vs. young adult mice after lethal irradiation and administration of T cell-depleted bone marrow (BM) from young mice. Abnormalities observed in aged thymi (reduced thymocyte numbers, histologic abnormalities) were not reversed by administration of young BM via bone marrow transplantation (BMT), but aged thymi displayed a normal thymocyte subset distribution and appropriately deleted MIs-reactive T cells after BMT. Aged BMT recipients regenerated significantly reduced numbers of splenic T cells compared to young recipients and showed increased peripheral expansion of thymic emigrants since a higher proportion of BM-derived T cells expressed a memory phenotype in aged vs. young BMT recipients. Because peripheral expansion of thymic emigrants could substantially increase the number of thymic progeny present in the spleen, we sought to measure thymic T cell regenerative capacity after BMT in a setting devoid of peripheral expansion. To do this, TCR-transgenic (Tg+) T cell-depleted BM was administered to aged and young recipients lacking antigen specific for the Tg+ TCR. Aged recipients regenerated approximately 50 % of the TCR Tg+ cells regenerated in young BMT recipients, providing evidence that even very aged thymi retain the capacity to regenerate significant numbers of mature T cell progeny. Therefore, thymic function is reduced with aged but it is not lost, suggesting that therapeutic approaches to enhance thymic function may be successful even in very aged hosts.

journal_name

Eur J Immunol

journal_title

European journal of immunology

authors

Mackall CL,Punt JA,Morgan P,Farr AG,Gress RE

doi

10.1002/(SICI)1521-4141(199806)28:06<1886::AID-IMM

subject

Has Abstract

pub_date

1998-06-01 00:00:00

pages

1886-93

issue

eissn

0014-2980

issn

1521-4141

pii

10.1002/(SICI)1521-4141(199806)28:06<1886::AID-IMM

journal_volume

pub_type

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Thymic function in young/old chimeras: substantial thymic T cell regenerative capacity despite irreversible age-associated thymic involution.