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Abstract
Objective
Alterations in the immune system occur with aging, and these contribute to an increased risk of infection and malignancy. The age-associated changes in T cell immunity range from single cell function to the maintenance of cell populations. We investigated the kinetics of CD4＋ T cell activation and proliferation in young and elderly subjects after stimulating their peripheral blood mononuclear cells with anti-CD3 and anti-CD28 antibodies (Abs).
Methods
The expressions of the activation markers CD69, CD40L and CD25 on the CD4＋ T cells from young (n=14) and elderly (n=19) were analyzed at 6, 24 and 48 hours (hrs) of T cell receptor (TCR) stimulation by using flow cytometry. In the same individuals, the CD4＋ T cell proliferation was determined at 48 and 96 hrs of TCR stimulation by using the CFSE dilution method.
Results
The elderly had decreased CD69 and CD40L expressions on the CD4＋ T cells at 6 hrs of stimulation, as compared to that of the young patients. The elderly also had a decreased CD25 expression on the CD4＋ T cells at 24 hrs of stimulation. However, the two groups had similar levels of the CD25, CD69 and CD40L expressions at 48 hrs of stimulation. The elderly had decreased CD4＋ T cell proliferation at 96 hrs of stimulation, as compared to that of the young, although both groups had similar levels of CD4＋ T cell proliferation at 48 hrs of stimulation.
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 | Fig. 1.The expressions of CD 69, CD40L and CD25 by the CD4＋ T cells in response to anti-CD3 and －CD28 antibody (Ab) stimulation. Peripheral blood mononuclear cells from a young individual and an elderly individual were stimulated for 6, 24 and 48 hours (hr) with PBS (thin line) or anti-CD3 Abs (bold line) at 10 μg/mL in the presence of anti-CD28 Abs (1 μg/ mL). The stimulated cells were stained with anti-CD4, －CD69 (A), －CD 40L (B) or －CD25 (C) Abs. The cells were washed and then analyzed on a flow cytometer. The cells were gated on the CD4＋ population. |
 | Fig. 2.Kinetics of the activation markers' expressions on the CD4＋ T cells in young and elderly people. Peripheral blood mononuclear cells from 14 young people and 19 elderly people were stimulated for 6, 24 and 48 hours (hr) with PBS or anti-CD3 Abs at 10 μg/mL in the presence of anti-CD28 Abs (1 μg/mL). The stimulated cells were stained with anti-CD4, －CD69 (A), －CD40L (B) or －CD25 (C) Abs. The cells were washed and analyzed on a flow cytometer. The cells were gated on the CD4＋ population. The differences in median fluorescent intensity (ΔMFI) between the samples stimulated with PBS and anti-CD3 Abs were obtained. The symbols and the error bars indicate the mean ΔMFI and the S.E.M, respectively. The values on the Y-axis indicate the ΔMFI. The p-values were obtained by the Mann-Whitney U test. |
 | Fig. 3.The proliferation of CD4＋ T cells in response to anti-CD3 and －CD28 antibody (Ab) stimulation as measured by carboxyfluorescein succinimidyle ester (CFSE) staining. The peripheral blood mononuclear cells from a young individual and an elderly individual were stained with CFSE. The cells were then stimulated for 48 (A) and 96 (B) hours (hr) with PBS (thin line) or anti-CD3 Abs (bold line) at 10 μg/mL in the presence of anti-CD28 Abs (1 μg/mL). The stimulated cells were stained with anti-CD4 Abs, washed and analyzed on a flow cytometer. The cells were gated on the CD4＋ population. The numbers on the histograms indicate the percentage of proliferated cells in the samples stimulated with anti-CD3 Abs. |
 | Fig. 4.Difference in the proliferation of CD4＋ T cells in response to anti-CD3 and －CD28 Ab stimulation between the young and the elderly. Peripheral blood mononuclear cells (PBMCs) from young and elderly people were stained with CFSE. The cells were then stimulated for 48 or 96 hours (hr) with PBS or anti-CD3 Abs at 10 μg/mL in the presence of anti-CD28 Abs (1 μg/mL). The stimulated cells were stained with anti-CD4 Abs. The cells were washed and analyzed on a flow cytometer. The data for 48 hr were from 7 young and 7 elderly individuals (A). The data for 96 hr were from 14 young and 16 elderly individuals (A and B). The columns and the error bars indicate the mean percent of proliferating CD4＋ T cells and the S.E.M (A) or the number of mean divisions and S.E.M (B). The p-values were obtained by the Mann-Whitney U test. |
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