Vv. Yurovsky et al., T-CELL REPERTOIRE IN THE BLOOD AND LUNGS OF ATOPIC ASTHMATICS BEFORE AND AFTER RAGWEED CHALLENGE, American journal of respiratory cell and molecular biology, 18(3), 1998, pp. 370-383
T cells play a pivotal role in initiating and orchestrating allergic r
esponses 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, differ
entials, and T-cell subsets in bronchoalveolar lavage (BAL) fluids sho
wed that ragweed challenge was associated with preferential recruitmen
t of CD4+ T cells into the lungs. A reverse transcriptase-polymerase c
hain reaction (RT-PCR) was used to amplify T-cell receptor (TCR) gene
transcripts from unfractionated, CD4(+) and CD8(+) T cells in blood an
d BAL fluids. As judged by RT-PCR, the usage of TCR Vol and VP gene fa
milies in BAL fluids was similar to that in blood. Ragweed challenge d
id not change the levels of expression of these V gene families, The c
lonality of T cells was estimated by analyzing the diversity of TCR V-
(D)-J junctional region nucleotide lengths associated with each Vol an
d VP gene family, using sequencing gel electrophoresis. Most V gene fa
milies in blood and BAL fluids were associated with multiple junctiona
l region lengths before and after ragweed challenge, indicating polycl
onal expression. Some V gene families were expressed in an oligoclonal
manner in unfractionated, CD4(+), and CD8(+) T cells in BAL fluids be
fore ragweed challenge, as indicated by a few predominant junctional r
egion lengths. The majority of these V gene families became polyclonal
after challenge, compatible with polyclonal T-cell influx during infl
ammation immediately after ragweed challenge, However, some V gene fam
ilies became oligoclonal or developed a new oligoclonal pattern of jun
ctional region lengths in BAL T cells after ragweed challenge. Surpris
ingly, this occurred in both CD4(+) and CD8(+) T cells. In one of thes
e instances. DNA sequencing of V beta 21 junctional regions in CD8(+)
T cells confirmed a change from polyclonal to oligoclonal expression a
fter ragweed challenge. These findings show that ragweed challenge is
associated with polyclonal influx and oligoclonal activation of both C
D4(+) and CD8(+) T cells in the lungs.