Important note: Information in this article was accurate in 1998. The state of the art may have changed since the publication date.
T-Cell repertoire in the blood and lungs of atopic asthmatics before and after ragweed challenge.
Am J Respir Cell Mol Biol. 1998 Mar;18(3):370-83. Unique Identifier : AIDSLINE MED/98158673 Yurovsky VV; Weersink EJ; Meltzer SS; Moore WC; Postma DS; Bleecker ER; White B; Department of Medicine, University of Maryland, Baltimore, Maryland; 21201, USA. vyurovsk@umabnet.ab.umd.edu
Abstract:
T cells play a pivotal role in initiating and orchestrating allergic responses in asthma. The goal of this work was to learn whether ragweed challenge in the lungs alters the T-cell repertoire expressed in the blood and lungs of atopic asthmatics. Analyses of cell numbers, differentials, and T-cell subsets in bronchoalveolar lavage (BAL) fluids showed that ragweed challenge was associated with preferential recruitment of CD4+ T cells into the lungs. A reverse transcriptase-polymerase chain reaction RT-PCR) was used to amplify T-cell receptor (TCR) gene transcripts from unfractionated, CD4+, and CD8+ T cells in blood and BAL fluids. As judged by RT-PCR, the usage of TCR Valpha and Vbeta gene families in BAL fluids was similar to that in blood. Ragweed challenge did not change the levels of expression of these V gene families. The clonality of T cells was estimated by analyzing the diversity of TCR V-(D)-J junctional region nucleotide lengths associated with each Valpha and Vbeta gene family, using sequencing gel electrophoresis. Most V gene families in blood and BAL fluids were associated with multiple junctional region lengths before and after ragweed challenge, indicating polyclonal expression. Some V gene families were expressed in an oligoclonal manner in unfractionated, CD4+, and CD8+ T cells in BAL fluids before ragweed challenge, as indicated by a few predominant junctional region lengths. The majority of these V gene families became polyclonal after challenge, compatible with polyclonal T-cell influx during inflammation immediately after ragweed challenge. However, some V gene families became oligoclonal or developed a new oligoclonal pattern of junctional region lengths in BAL T cells after ragweed challenge. Surprisingly, this occurred in both CD4+ and CD8+ T cells. In one of these instances, DNA sequencing of Vbeta21 junctional regions in CD8+ T cells confirmed a change from polyclonal to oligoclonal expression after ragweed challenge. These findings show that ragweed challenge is associated with polyclonal influx and oligoclonal activation of both CD4+ and CD8+ T cells in the lungs.
Keywords: *Asthma/IMMUNOLOGY *Hypersensitivity, Immediate/IMMUNOLOGY *Lung/IMMUNOLOGY *Receptors, Antigen, T-Cell, alpha-beta/GENETICS *T-Lymphocytes/IMMUNOLOGY 980630
M9861856
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