An imbalance of naive and memory/effector subsets and altered expression of CD38 on T lymphocytes in two girls with hyper-IgM syndrome

Abstract

SUMMARY In this report we evaluated CD4+ T, CD8+ T and natural killer (NK) cell counts, the levels of naive/memory subsets within the CD4+ T lymphocyte population, expression of CD38 on T lymphocytes, and CD4+ and CD8+ T cell cytokine production in two girls with hyper-IgM (HIM) syndrome. Both girls developed recurrent infections early in infancy, presenting a wide spectrum of clinical manifestations, with a strikingly different disease severity between them. CD4+ T cell counts were low in both children (patient 1: 214 cells/mm3 and patient 2: 392 cells/mm3), and the CD4/CD8 T cell ratio was 0·4 for patient 1, the patient with the more severe disease, and 1·4 for patient 2. NK cell numbers were low in patient 1 (60 cells/mm3) and borderline (286 cells/mm3) with regard to normal levels in patient 2. An imbalance of naive and memory/effector cell subsets was found in both girls, with the percentage of CD45RA+ 27+ (naive) CD4+ T lymphocytes being 5·8 and 12·4 for patients 1 and 2, respectively. Expression of CD38 on the surface of T lymphocytes was low in patient 1. Detection of intracellular interferon (IFN)-γ and tumour necrosis factor (TNF)-α in CD4+ and CD8+ T lymphocytes upon PMA-Io stimulus was preserved in both children. In conclusion, we found low numbers of CD4+ T lymphocytes and a dramatic redistribution of naive and memory/effector CD4+ T lymphocytes in two girls with non-X-linked HIM syndrome. Furthermore, we found low expression of CD38 on T lymphocytes and low numbers of NK cells in the patient with the more severe disease, indicating a possible role for these cells in the pathogenesis of this immunodeficiency.