Mechanic and colleagues described 17 hypogammaglobulinemic patients with common variable immunodeficiency who had a granulomatous disease [1]. They found that 16 of 17 patients had deficient T-cell proliferation to mitogens, a finding suggesting that impaired T-cell function may lead to the abnormal sequestration of antigen and the subsequent formation of granulomas. In this regard the analysis of the T cells, which are classically CD4^- CD8^- double-negative and whose involvement in granulomatous disease has already been shown [2], could be informative.

As an example, we describe a 31-year-old woman in whom common variable immunodeficiency was diagnosed in April 1995. The patient was seen in July 1996 reporting recent weight loss and a 2-year history of chronic diarrhea. Clinical investigations disclosed a steatorrhea and protein-losing enteropathy. Computed tomography of the abdomen showed mesenteric and retroperitoneal masses, interpreted as necrosed lymphadenopathies. Histologic examination of lymphadenopathy biopsy specimens showed epithelioid cell granulomas with polynucleated giant cells without caseous necrosis. Smears stained with Ziehl-Neelsen were positive for acid-fast bacilli, whereas culture and polymerase chain reaction remained negative for tuberculous and nontuberculous mycobacteria. Thus, the diagnosis of mycobacterial infection was never confirmed.

The patient was lymphopenic (lymphocyte count, 364 cells/mm³), and the T-cell subsets, determined by flow cytometry [3], were as follows: CD3⁺, 240 cells/mm³ (66%); CD4⁺, 13 cells/mm³ (3.60%); CD8⁺, 86 cells/mm³ (23.60%); and CD3⁺ double-negative, 140 cells/mm³ (39%). These double-negative T lymphocytes were expressing the T-cell receptor primarily by using the variable gene segments V 9 VDelta2 (138 cells/mm³, 38%). This percentage of double-negative T cells among total peripheral lymphocytes was grossly elevated compared with the percentage in 57 healthy donors (median, 2.1% [range, 0.6% to 8.2%]) [3]. Antimycobacterial therapy against tuberculous and nontuberculous mycobacteria was begun, with a poor clinical result. After 9 months of treatment, lymphadenopathy persisted and the percentage of double-negative T cells had not decreased (35%).

In view of studies describing in vivo and in vitro activation of cells by microorganisms [3-5], we suggest that T cells are of clinical interest because their expansion may be viewed as a way to alleviate the impaired T-cell-mediated immunity in patients with common variable deficiency in whom the cause of granulomas remains elusive.