T-cell repertoire in the blood and lungs of atopic asthmatics before and after ragweed challenge

Vladimir V. Yurovsky, Els J.M. Weersink, Susan S. Meltzer, Wendy C. Moore, Dirkje S. Postma, Eugene R. Bleecker, Barbara White

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


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 Vα and Vβ 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 Vα and Vβ 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 polydonal 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 Vβ21 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.

Original languageEnglish (US)
Pages (from-to)370-383
Number of pages14
JournalAmerican journal of respiratory cell and molecular biology
Issue number3
StatePublished - 1998
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology


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