CD4⁺Treg in Immune Pathophysiology of Aplastic Anemia.

Objective: To explore the possible immune pathophysiology of CD4⁺T regulatory (CD4⁺Treg) in acquired aplastic anemia (AA).

Methods: According to the markers on membrane, cytokines, and effective mechanisms of CD4⁺Treg, the levels of CD4⁺CD25⁺Treg,CD4⁺CTLA-4⁺Treg,CD4⁺ICOS⁺Treg,CD4⁺PD-1⁺Treg,CD3⁺CD8⁻IL-10⁺Treg,CD3⁺CD8⁻TGF-β1⁺Treg,CD3⁺CD8⁻IL-Treg in the bone marrow of 23 cases with AA at active phase, 10cases with AA at recovery phase, 15 normal controls, were measured, and the relationship between CD4⁺Treg and priming immune factor-CD28 or effective immune factor-IFN-γ were also evaluated respectively.

Results: [circ1]In the group of AA at active phase, at recovery phase, and normal controls, CD4⁺CD25⁺Treg: (3.36±2.05)%, (3.49±1.71)%, (2.40±0.77)%, CD4⁺CTLA-4⁺ Treg: (1.43±0.67)%, (3.46±2.26)%, (2.45±1.30)%, CD4⁺ICOS⁺Treg: (2.04±1.79)%, (2.95±2.23)%, (2.37±1.68)%, CD4⁺PD-1⁺Treg: (1.40±1.32)%, (2.34±0.87)%, (2.07±1.64)%, CD3⁺CD8⁻IL-10⁺Treg: (2.14±1.19)%, (2.37±1.20)%, (2.04±1.25)%, CD3⁺CD8⁻TGF-β1⁺Treg: (1.83±0.99)%, (1.52±0.73)%, (2.15±1.17)%, CD3⁺CD8⁻IL-4⁺Treg: (2.46±1.65)%, (2.53±1.61)%, (1.99±1.27)%; costimulatory of CD3⁺CD4⁺CD28⁺ was: (39.84±10.89)%, (22.72±9.08)%, 31.40±10.83)%, the Th1cells CD3⁺CD8⁻IFN-γ⁺ were: (11.13±4.96)%, (5.39±4.29)%, (4.21±2.11)%. [circ2] Contrast to normal controls, while CD4⁺CTLA-4⁺Treg of AA at active phase deceased markedly (p=<0.01), levels of other CD4⁺Treg which marked by membrane moleculars or cytokines: CD4⁺CD25⁺Treg, CD4⁺PD-1⁺Treg, CD4⁺ICOS⁺Treg, CD3⁺CD8⁻IL-10⁺Treg, CD3⁺CD8⁻TGF-β1⁺Treg, CD3⁺CD8⁻IL-4⁺Treg did not change significantly (p>0.05); [circ3] Contrast to normal controls, the ratio of membrane costimulatory of CD28/ICOS CD28/CTLA-4, CD28/PD-1 were all increased significantly (p<0.05) in AA at active phase; the ratio of cytokines in cell plasma of IFN-γ⁺IL-4, IFN-γ/TGF-β, and IFN-γ/IL-10, were also increased significantly (p<0.05).

Conclusion: [circ1] In AA, the positive regulatory costimulatory increased while the negative regulatory costimulatory did not change or decreased, which shifted the immune balance to intensification. [circ2] Not only at priming stage but also at effective stage, the immune strengthened factors were higher than attenuated factors in AA.