Studies on the T cell receptor BV repertoire in relation to asthma

In this thesis the TCR BV repertoire of the lung and peripheral blood of asthmatic and non-atopic asthmatic individuals was investigated using flow cytometry and molecular biology methods.In both the peripheral blood and bronchoalveolar lavage (BAL) derived from lung of normal and asthmatic individuals the TCR BV repertoire did not differ greatly. Certain TCR BV families tended to be expressed at low or high levels in both compartments in the CD3+, CD4+ and CD8+ T cell subsets. Of note, BV7S1 was the BV subfamily expressed at the lowest levels in all T cell subsets in blood and BAL. BV5S2/3 was also expressed at higher levels in the BAL of asthmatics compared to the blood.There were no consistent changes in TCR BV expression in either peripheral blood or BAL 24 hours after allergen challenge to the lungs of atopic asthmatics. Although the numbers of eosinophils and neutrophils increased there was no change in the levels of CD3+, CD4+ and CD8+ cells after challenge. From the results obtained from flow cytometry overall, it was concluded that there were no significant differences quantitatively in TCR BV expression and that it would be interesting to examine the clonality and CDR3 sequences of individual TCR BV families.It was concluded from the above studies that the clonality of TCR BV populations is not dependent on levels of expression. The T cell population in the lung is not isolated from that in the blood and oligoclonal populations are present in the lung normally, even in non-asthmatics. TCR BV repertoires also appear to be individual specific. It would have been interesting to examine the clonality and CDR3 sequences of greater numbers of TCR BV families and to investigate clonality within the CD4+ and CD8+ subsets.