Oligoclonal T cell proliferative disorder in combined immunodeficiency

Oligoclonal lymphoid proliferations may occur in immunocompromised patients and in the elderly. So far these proliferations have been shown to be of B cell origin. We describe a patient with a combined immunodeficiency, characterized by profound hypogammaglobulinemia and the initial absence of T lymphocytes in the peripheral blood (PB). From the age of 4 yr CD3+ T cells appeared in PB in rising numbers. These cells mainly expressed the CD4-/CD8+ phenotype (CD4/CD8 ratio: 0.1). Despite the emergence of T lymphocytes no proliferation of PB mononuclear cells could be induced with phytohemagglutinin, concanavalin A, or pokeweed mitogen. Between the ages of 4 and 6 yr the patient gradually developed hepatosplenomegaly and an interstitial pulmonary infiltrate of unknown origin, necessitating biopsies of both liver and lung. Infiltrates consisting of CD8+ T lymphocytes were found in the liver as well as the lung. CD8+ T cells were also abundant in the bronchoalveolar lavage fluid. Southern blot analysis of mononuclear cells from PB and of a lung biopsy specimen was performed to investigate if a clonal T cell population was involved. Analysis of the T cell receptor beta genes revealed that at least three expanded T cell clones were present in PB, one of which had invaded the lung. Thus far, i.e. 2 yr after the initial detection of clonal T cell receptor beta gene rearrangements, there have been no clinical or histologic signs of malignant behavior. We conclude that this combined immunodeficiency patient has a benign oligoclonal T cell lymphoproliferative disorder. Similar proliferations might well occur in other immunodeficiency states, whether primary or acquired.