Category: Immunodeficiency: primary or acquired
CD40 ligand (CD40L) deficiency is an X-linked primary immunodeficiency, associated with the opportunistic infection and increased rate of malignancy. CD40L is expressed primarily on the activated CD4+ T lymphocytes which interacts with CD40 expressed on various immune cells. CD40-CD40L engagement regulates the innate, cellular and humoral immunities including recall memory function of CD8+ T lymphocytes. Alternations in T cell immunity occur with aging, likely contributing to increased infections and malignancies. Aging increases the frequency of memory CD8+ T lymphocytes, especially those expressing high and low levels of CD57 and IL-7Rα, respectively. Here we addressed the hypothesis that early CD8+ T lymphocytes senescence occurs in CD40L deficiency by analyzing the frequency, phenotypic and functional characteristics of peripheral CD8+ T lymphocytes subsets in a family with a novel CD40L mutation and healthy controls (HCs) using flow cytometry and high-dimensional mass cytometry (CyTOF). The five-year-old CD40L deficiency male patient and his twenty-one-year-old mother with the heterozygous mutation had an increased frequency of effector memory (EM) CD8+ T lymphocytes expressing high and low levels of CD57 and IL-7Rα, respectively, and higher levels of IFN-γ, IL-13 and granzyme B production in IL-7Rα low EM CD8+ T lymphocytes compared to age-matched and middle age HCs (age 40-65). The patient had persistently increased frequency of IL7Rαlow EM CD8+ T lymphocytes even in the absence of active infection and on stable IVIG therapy. Our findings suggest the development of early CD8 senescence in CD40L deficiency despite IVIG therapy restoring humoral immunity.
Junghee Shin– clinical fellow, Yale University School of medicine
Insoo Kang– Associate proferssor, Yale University, School of Medicine
Jason Catanzaro– Clinical instructor, Yale University, Pediatrics
Min Sun Shin– Associate scientist, Yale University, School of Medicine
Neil Romberg– physician, Children's hospital of philadelpia
Paula Whittington– Yale University, School of Medicine