Study of CD28 Costimulatory Super Family and CD4⁺Treg in Myelodysplastic Syndromes.

Objective: To explore the possible immune annormality of CD28 costimulatory super family and CD4⁺T regulatory (CD4⁺Treg) in myelodysplastic syndrome (MDS).

Methods: Gated by CD3 and SSC, the changes of CD28, CTLA-4, PD-1, and CD25, on CD3⁺CD4⁺ cells were evaluated in 38 new diagnosed cases with MDS(RA 17, RAS 1, RAEB 14, RAEB-t 6) and 11 normal controls respectively by directive immune labels.

Results: [circ1]In the group of MDS, the CD3⁺CD4⁺CD28⁺ was 79.82%±8.99% ( RA 78.65%±10.4%, RAEB/RAEB-t 80.10%±7.28% respectively), was lower than 89.56%±3.06% of normal controls (P<0.01); CD3⁺CD4⁺CTLA-4⁺, CD3⁺CD4⁺PD-1⁺, and CD3⁺CD4⁺CD25⁺ were 2.14%±1.25% (RA 1.51%±0.80%, RAEB/RAEB-t 2.65%±1.33%), 1.44%±0.88% (RA 0.93%±0.63%, RAEB/RAEB-t 2.02%±0.76%), and 3.18%±2.11%(RA 2.80%±1.38%, RAEB/ RAEB-t 3.41%±2.46%) in MDS, which were all higher than those (0.11%±0.12%, 0.09%±0.14% and 1.65%±1.14% respectively) of normal controls (P<0.01). [circ2] Along with the progress of MDS, the expression of CTLA-4, PD-1 and CD25 on CD3⁺CD4⁺ cells increased significantly in RAEB/RAEB-t than RA. [circ3] The antagonism costimulatory of CTLA-4/CD28 decreased from normal controls (0.11±0.11) to RA (2.14±0.97), then to RAEB/RAEB-t (3.58±1.55) significantly.

Conclusion: [circ1] In MDS, the immune priming factor-CD28 decreased while the suppressive factor-CTLA-4 increased. [circ2] The negative immune CD4⁺ regulatory increased in MDS, and was predominance in immune balance. [circ3] Along with progression of MDS, negative regulatory factors was enforced, which promoted clone of MDS expansion.