Chemokine gene expression and clonal analysis of B cells in tissues involved by lymphoid interstitial pneumonitis from HIV-infected pediatric patients

Lymphoid interstitial pneumonitis (LIP), a frequent pulmonary complicationi ni HIV-infected pediatric patients, is characterized histologically by mark ed infiltration of lymphoid cells. We sought to evaluate the nature and pat hogenesis of the lymphoid infiltrates and to examine the relationship of UP to pulmonary MALT lymphoma that has been described in pediatric HIV positi ve patients. To examine the potential contribution of chemokines and cytoki nes to the inflammatory cell recruitment in tissues involved by lymphoid in terstitial pneumonitis from HIV-infected pediatric patients, RNA was extrac ted from paraffin-embedded tissues from five lung biopsies in four pediatri c HIV-positive patients and from five control, normal lung biopsies in five HIV-negative patients and was analyzed by semiquantitative RT-PCR for the expression of cytokines (TNF-alpha, GM-CSF, IFN-gamma, IL-4, IL-6, IL-10, a nd IL-18) and chemokines (IL-10, Mig, regulated upon activation, normal T e xpressed and secreted [RANTES], and MIP1-alpha and beta) after normalizatio n for G3PDH. Expression of IL-18 was increased, as well as expression of IF N-gamma -inducible chemokines IP-10 and Mig in LIP tissues compared with co ntrols. RANTES and MIP1-alpha and -beta were also increased in pediatric UP lesions compared with controls. In contrast, expression of TNF-alpha, GM-C SF, IL-10, and IL-6 was variable in UP tissues and controls. In addition, c lonality of the B-cell population was evaluated by VDJ-PCR. A polyclonal B- cell population was shown hi all five biopsies from five patients with LIP; and in one patient with concurrent LIP and MALT lymphoma, a band of increa sed intensity was observed in the LIP biopsy that was identical in size to the monoclonal band In the concurrent MALT lymphoma biopsy. These results p rovide evidence of high-level expression of certain chemokines in lymphoid interstitial pneumonitis tissues and suggest that chemokines and cytokines may play an important role in the recruitment of inflammatory cell infiltra tes into these tissues. In addition, UP may represent an early stage of MAL T lymphoma or an immunologic response to a chronic antigenic stimulus that may provide a milieu or microenvironment for the evolution of a monoclonal B-cell population.