Flow cytometric assessment of T cell activation in asthma

The results of this thesis show that asthmatics have an increased percentage of CD4+ T cells in blood and a tendency for a decreased percentage of CD8+ T cells in both blood and BAL compared to healthy controls, whilst steroid treated asthmatics showed a decreased CD4/CD8 ratio in BAL compared to non steroid treated asthmatics. No differences were observed between asthmatic and normal CD3+ or CD4+ T cells expressing CD25 or HLA-DR. However steroid treated asthmatics had a decreased percentage of CD4+ BAL T cells which expressed CD25. Although few blood or BAL CD8+ T cells expressed CD25, increased percentages were observed in non-steroid treated asthmatics. BAL T cells had reduced MIF of ICAM-1 expression 6 hours after allergen challenge. Neither allergen challenge nor rhinovirus infection induced changes in the percentage of T cells expressing CD25 or HLA-DR, however six hours after allergen challenges there was a significant reduction in CD3+ cells in the blood which remained low at 24 hours. A similar decrease in CD3+ blood cells was also observed 3 days after HRV16 infection.IFNγ production was found to be more frequently associated with CD4+ T cells compared T CD8+ T cells in asthmatic blood, however in BAL IFNγ production was more frequently associated with CD8+ T cells. Furthermore in blood the activation markers CD25 and HLA-DR were found to be unassociated with cytokine production whereas in BAL T cells HLA-DR was partially associated with cytokine production.In conclusion it appears that the classical T cell activation markers CD25 and HLA-DR are unaltered in asthma. However there are differences between normal and asthmatic T cell IFNγ production which is altered by allergen challenge and not associated with CD25 surface marker expression. Therefore T cell activation does appear to play a role in asthmatic inflammation, however these studies cast doubt on the theory that asthma is a Th2 disease and opens up debate about the role of IFNγ in asthma.