A Novel Thymoma-Associated Immunodeficiency with Increased Naive T Cells and Reduced CD247 Expression

The mechanisms underlying thymoma-associated immunodeficiency are largely unknown, and the significance of increased blood gamma delta T. cells often remains elusive. In this study we address these questions based on an index patient with thymoma, chronic visceral leishmaniasis, myasthenia gravis, and a marked increase of rare gamma delta T cell subsets in the peripheral blood. This patient showed cutaneous anergy, even though he had normal numbers of peripheral blood total lymphocytes as well as CD4(+) and CD8(+) T cells. Despite his chronic infection, analyses of immunophenotypes and spectratyping of his lymphocytes revealed an unusual accumulation of naive gamma delta and alpha beta T cells, suggesting a generalized T cell activation defect. Functional studies in vitro demonstrated substantially diminished IL-2 and IFN-gamma production following TCR stimulation of his untouched naive CD4(+) T cells. Biochemical analysis revealed that his gamma delta and alpha beta T cells carried an altered TCR complex with reduced amounts of the zeta-chain (CD247). No mutations were found in the CD247 gene that encodes the homodimeric zeta protein. The diminished presence of CD247 and increased numbers of gamma delta T cells were also observed in thymocyte populations obtained from three other thymoma patients. Thus, our findings describe a novel type of a clinically relevant acquired T cell immunodeficiency in thymoma patients that is distinct from Good's syndrome. Its characteristics are an accumulation of CD247-deficient, hyporresponsive naive gamma delta and alpha beta T cells and an increased susceptibility to infections.