Distinctive CD8+ T cell and MHC class I signatures in polycythemia vera patients

Abstract

Polycythemia vera (PV) is a myeloproliferative neoplasm characterized by overproduction of red blood cells. We have performed a comprehensive characterization of blood immune cells for expression of naïve and memory receptors as well as β₂m-associated and β₂m-free MHC class I heavy chains, also known as closed and open conformers, respectively, in PV patients and age-matched controls (CTR). We show that the peripheral CD3⁺CD8⁺ T cell pool in PV patients is clearly divided into two discrete populations, a more granular CD3⁺CD8^high T cell population enriched in effector-memory CD45RA⁺ T cells (CD8⁺ TEMRA) when compared to CTR (P < 0.001), and a less granular CD3⁺CD8^int T cell population that is completely absent in the CTR group (78 vs. 0%, P < 0.001) and is a mixture of naïve (CD8⁺ T_N) and CD8⁺ TEMRA cells expressing intermediate levels of CD28, i.e., CD3⁺CD8^intCD28^int. While the percentage of CD3⁺CD8^int TN cells correlated positively with the number of erythrocytes, the percentage of CD3⁺CD8^int TEMRA correlated negatively with the number of platelets. Finally, we report that PV patients' lymphocytes and monocytes display lower levels of closed (W6/32⁺) MHC-I conformers at the cell surface while exhibiting increased amounts of open (HC-10⁺) MHC-I conformers. The implications of this distinctive immune signature are discussed.

Keywords: CD3+CD8intCD28int; Effector-memory lymphocytes; JAK2; Myeloproliferative neoplasm; Open HLA class I conformers.