Background/Purpose:

Programmed death-1 (PD-1) has been regarded as a negative regulatory signal in T cells. Our laboratory has shown that PD-1 is important in T cell regulation of autoimmunity, as treatment with neutralizing anti-PD1 in the NZB/NZWF₁ mouse model of lupus increased regulatory T cell (T_reg) function and dramatically delayed SLE onset in young mice.

We hypothesized that SLE patients have increased PD-1 expression compared to healthy individuals, which may contribute to the compromised CD4⁺T_reg function in these patients.

Methods:

Forty-five female SLE patients and twenty healthy female controls have been enrolled to date. Medical chart review was done to assess SLE disease activity index (Selena SLEDAI) score. PD-1 expression on CD4⁺T_reg (defined as CD4⁺CD25^hiFoxp3⁺) from the PBMC collected on the same day of the chart note was analyzed by flow cytometry, as were samples from healthy donors. Statistical analysis was performed to assess the relationship between PD-1 expression and SLEDAI. CD4⁺T_reg from patients were treated with neutralizing anti-PD-1 in vitro to test for their ability to induce B cell apoptosis, and CD4⁺CD25^– helper T cell (T_h) proliferation.

Results:

SLE patients had fewer CD4⁺CD25^hiFoxp3⁺ T_reg in their PBMC compared to healthy controls (p <0.03), but these cells had significantly increased PD-1 expression (p<0.02). CD4⁺T_reg from patients with SLEDAI ≥ 4 tended to express more PD-1 than those from patients with SLEDAI <4 (p<0.07). Increased PD-1 expression was associated with vasculitis, thrombocytopenia and leukopenia (p <0.05). With in vitro PD-1 blockade, CD4⁺T_reg from the SLE patients were more resistant to apoptosis, and had increased ability to induce B cell apoptosis and to suppress T_h proliferation when compared to CD4⁺T_reg treated with IgG isotype. 

Conclusion:

SLE patients have aberrant, increased PD-1 expression on their circulating CD4⁺T_reg that may reduce the regulatory function of CD4⁺CD25^hiFoxp3⁺ T cells, which are important in the suppression of autoimmunity. One mechanism by which PD-1 sustains these T_reg is by reducing their susceptibility to apoptosis.

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« Back to 2013 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/reduced-pd-1-signaling-promotes-suppressive-function-of-cd4-regulatory-t-cells-in-patients-with-systemic-lupus-erythematosus/