Background/Purpose:

To investigate the apoptosis of CD4⁺T cell and Tregs in the pathogenesis and disease activity of rheumatoid arthritis patients.

Methods: Isolated lymphocytes from human peripheral blood, the expressive levels of Annexin V, Caspase-3/8, Fas and Bcl-2 of CD4⁺T lymphocytes and Tregs in RA patients and controls were analysed by using flow cytometry. The correlation between the apoptosis level, the apoptosis signaling proteins expression of CD4⁺T, Tregs and clinical activity parameters were analysed. The effects of IL-10 and anti-IL-10 were also observed.

Results:

1.   Compared with the controls, the level of CD4⁺T cells was higher in RA patients, while their apoptosis was lower (p<0.05); the frequency of Tregs was lower in RA patients, while their apoptosis was higher (p<0.05).

2.   Compared with the controls, the expression of Fas (p<0.01) and Caspase-8 (p<0.05) by CD4⁺T cells decreased in RA patients,the expression of Bcl-2 by CD4⁺ T cells (p<0.05) increased; the expression of Fas (p<0.01), Caspase-8 (p<0.05) and Caspase-3 (p<0.05) by Tregs elevated in RA patients.

3.   The expression of AnnexinV and Fas by CD4⁺T cells in RA patients were negatively correlated with DAS28 (r=-0.84, p<0.01 and r=-0.89, p<0.05, respectively), the expression of Bcl-2 by CD4⁺T cells was positively correlated with DAS28(r=0.91,p<0.01). There was positive correlation between the expression of Annexin V and Caspase-3 by Tregs and DAS28 in RA patients(r=0.82,p<0.01 and r=0.79,p<0.05, respectively).

4.   After IL-10 treatment, the apoptosis of CD4⁺ T cells increased (p<0.05), and that of Tregs decreased (p<0.05); the apoptosis of CD4⁺ T cells in anti-IL-10 group decreased (p<0.05), and that of Tregs increased (p<0.05); the expression of Caspase-8 by CD4⁺ T cells in IL-10 group increased (p<0.05), the expression of Bcl-2 by CD4⁺ T cells in IL-10 group decreased (p<0.05); the expression of Caspase-8 by CD4⁺ T cells in anti-IL-10 group was lower than that of the blank group (p<0.05), the expression of Bcl-2 by CD4⁺T cells in anti-IL-10 group was higher (p<0.05); the expression of Caspase-8/3 by Tregs in IL-10 group decreased (p<0.01), while the expression of Caspase-8/3 by Tregs in anti-IL-10 group was significantly elevated than that of the blank group (p<0.01).

Conclusion:

1.   The higher level of CD4⁺ T cells and the lower frequency of Tregs may be caused by the decreased apoptosis of CD4⁺ T cells and the increased apoptosis of Tregs, which may be the reason of the abnormal autoimmune response in RA.

2.   Fas, Caspase-8 and Bcl-2 may play a role in the the apoptosis of CD4⁺T cells. The apoptosis of Tregs may be related to the higher expression of Fas, Caspase-8/3.

3.   The expression of AnneinV, Fas and Bcl-2 by CD4⁺T cells and the expression of AnnexinV and Caspase-3 by Tregs in RA patients might be sensitive indicators of the clinical activity of RA.

4.   IL-10 has different immunoregulatory functions in different cells. It can downregulate the expression of Bcl-2, stimulate the expression of Caspase-8 in CD4⁺ T cells and inhibit the expression of Caspase-8/3 in Tregs of RA patients.

ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-significance-of-the-apoptosis-level-and-the-apoptosis-related-signal-proteins-of-cd4t%ef%bf%bdacd4foxp3t-cell-in-patients-with-rheumatoid-arthritis/