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T-cell cytotoxicity and aging: differing causes of reduced response in individual mice.

Abstract：

:Specific T-cell cytotoxic responses to allogeneic and hapten-modified syngeneic cells decrease with age. In order to determine the causes of these reduced T-cell cytotoxic responses, spleen cells from individual young and senescent C57BL/6J female mice were mixed in various proportions in culture with either X-irradiated BALB/c spleen cells or trinitrophenyl-modified syngeneic cells and the resultant cytotoxic responses determined in comparison to those of spleen cells from young and old mice stimulated alone. In both allogeneic and hapten-modified syngeneic cytotoxicity, it was found that a low percentage of the aged mice suffered from decreased helper-cell activity or from increase of suppressor activity, while the majority of mice showed no synergy, positive or negative, with the cells from the young donor. Studies of interleukin-2 (IL-2) activity were performed on conditioned medium from spleen cells from mice of various ages cultured for 24 h with concanavalin A. Those preparations from senescent mice that showed reduced IL-2 activity did not contain activity suppressive or competitive to IL-2 produced by spleen cells from young mice. Limiting dilution of spleen cells from mice of various ages in the presence of semi-allogeneic stimulatory cells and subsequent assay of the resultant allogeneic cytotoxicity provided a measure of the frequency of cytotoxic units. Parallel experiments in which crude IL-2 was added to the limit dilution cultures provided a measure of the frequency of cytotoxic cell precursors. Once again in these experiments, individual senescent mice demonstrated different defects. Three different types of age-related defects were observed. Certain aged mice were devoid of detectable cytotoxic units and cytotoxic T-lymphocyte precursor at the cell dilutions used. Other senescent mice demonstrated a very low frequency of cytotoxic units (approximately 1/40 000) as compared with young mice (approximately 1/5 000), and the addition of crude IL-2 to cultures from these mice did not improve reactivity. A third group of old mice, those with a moderate age-related decrease in the frequency of cytotoxic units (approximately 1/12 000), demonstrated a cytotoxic T-lymphocyte precursor frequency in the presence of crude IL-2 which was comparable to that of young mice (approximately 1/1000).

journal_name

Mech Ageing Dev

journal_title

Mechanisms of ageing and development

authors

Zharhary D,Segev Y,Gershon HE

doi

10.1016/0047-6374(84)90135-0

subject

Has Abstract

pub_date

1984-04-01 00:00:00

pages

129-40

issue

1-2

eissn

0047-6374

issn

1872-6216

pii

0047-6374(84)90135-0

journal_volume

pub_type

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T-cell cytotoxicity and aging: differing causes of reduced response in individual mice.