Am. J. Respir. Crit. Care Med., Volume 165, Number 2, January 2002, 254-259

Oligoclonal T Cell Expansions in Pulmonary Lymphoproliferative Disorders
Demonstration of the Frequent Occurrence of Oligoclonal T Cells in Human Immunodeficiency Virus-Related Lymphoid Interstitial Pneumonia

KATSUSHI KUROSU, NORIO YUMOTO, WILLIAM N. ROM, YUICHI TAKIGUCHI, JAGIRDAR JAISHREE, KOH NAKATA, KOICHIRO TATSUMI, ATSUO MIKATA, TAKAYUKI KURIYAMA, and MICHAEL D. WEIDEN

Department of Respirology and Department of Pathology, School of Medicine, Chiba University, Chiba, Japan; Division of Pathology, Chibahokuso Hospital, Nippon Medical School, Japan; and Division of Pulmonary and Critical Care Medicine and Bellevue Chest Service and Department of Pathology, New York University Medical Center, New York, New York

We used a denaturing gradient gel electrophoresis (DGGE) procedure with 40-nucleotide guanine- and cytosine-rich sequences in the polymerase chain reaction (PCR) and sequencing analysis to analyze the T cell antigen receptor (TCR)-V gene repertoire of infiltrating T lymphocytes in pulmonary lymphoproliferative disorders. Six of 15 low-grade mucosa-associated lymphoid tissue (MALT) lymphomas and 8 of 15 cases of lymphocytic interstitial pneumonia (LIP) showed some oligoclonal bands for TCR-V genes on DGGE. Sequencing analysis demonstrated plural oligoclonal TCR-V clones among the oligoclonal PCR products on DGGE, leading to the conclusion that conventional antigen-specific oligoclonal expansions may play some role in the pathogenesis of pulmonary lymphoproliferative disorders. The frequency of oligoclonal infiltrating T cell expansions in human immunodeficiency virus (HIV)-related LIP (100%) was significantly higher than in low-grade pulmonary MALT lymphomas (40%) or in HIV-negative LIP (30%). Because recent evidence demonstrates that the V3 loop in the proviral amino acid sequences of mononuclear cells from bronchoalveolar lavage is more homogeneous than those from peripheral blood, this homogeneity might result in oligoclonal expansions of infiltrating T lymphocytes as a consequence of ongoing reactions against lung-specific viral strains.

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