AMPD3 may affect ADAM17 activity to cause T-cell phenotypes. (A) Hypothesis: Erythrocytes release ATP through a nonlytic pathway or intravascular hemolysis. Increased ATP content in Ampd3^−/− mouse serum activates Adam17, which triggers shedding of its substrates, including CD62L, from the T-cell surface. (B) MFI of TNFR1 on the surface of CD4⁺ and CD8⁺ T cells, as determined by flow cytometry; isotype antibody was used as control (n = 4 for Ampd3^−/− and wild-type). (C) Abundance of soluble TNFR1 was determined by ELISA from 2 dilutions of mice serum (n = 4 for wild-type and Ampd3^−/− mice). *P ≤ .05, **P ≤ .01. ns, not significant (P > .05); OD450, optical density at 450 nm.