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Insufficient interleukin‐2 production from splenic CD4 + T cells causes impaired cell proliferation and early apoptosis in SAMP1, a strain of senescence‐accelerated mouse
Author(s) -
Nishimura Yasumitsu,
Hosokawa Tomohide,
Hosono Masamichi,
Baba Mitsuo,
Hosokawa Masanori
Publication year - 2002
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.1365-2567.2002.01496.x
Subject(s) - biology , propidium iodide , interleukin 2 , apoptosis , microbiology and biotechnology , concanavalin a , senescence , cytokine , cell culture , cd28 , interferon gamma , t cell , medicine , endocrinology , programmed cell death , immunology , in vitro , biochemistry , immune system , genetics
Summary We examined the proliferative and cytokine‐producing activities of CD4 + T cells from young mice of the senescence‐accelerated mouse strain SAMP1, which had shown markedly low T‐dependent antibody‐producing responses. When splenic T cells were cultured with concanavalin A (Con A), the percentage of CD4 + cells decreased earlier in SAMP1 than in C3H/He mice. At 40 hr of culture, the percentage of BrdU‐labelled proliferating CD4 + cells increased strongly in C3H/He, but only slightly in SAMP1. When purified CD4 + T cells were cultured with Con A, the percentage of 5‐bromo‐2′‐deoxyuridine (BrdU)‐labelled cells peaked at around 48 hr of culture in both strains, but decreased significantly at 64 hr in SAMP1. The production of interleukin (IL)‐2 but not IL‐4 or interferon‐γ (IFN‐γ) was significantly lower in SAMP1 than in C3H/He at 48 hr of culture. IL‐2 production was also markedly low in SAMP1, even under the stimulation of anti‐CD3 with anti‐CD28 antibodies. The frequency of cells producing IL‐2 was significantly lower in SAMP1 than in C3H/He at 6–24 hr of culture with Con A. The percentage of annexin‐positive and propidium iodide (PI)‐negative apoptotic cells was significantly higher in SAMP1 than in C3H/He at 96 hr of culture. Exogenous IL‐2 prevented the decrease in BrdU‐labelled cells and the increase in apoptotic cells in the SAMP1 cell culture. These results indicate that SAMP1 CD4 + T cells cannot produce IL‐2 at levels sufficient to support cell proliferation and survival. This may account for the weak T‐dependent antibody response in SAMP1 mice.