Expansion of CD4 + CD25 + and CD25- T-Bet, GATA-3, Foxp3 and RORγt Cells in Allergic Inflammation, Local Lung Distribution and Chemokine Gene Expression.

• Allergic asthma is associated with airway eosinophilia, which is regulated by different T-effector cells. T cells express transcription factors T-bet, GATA-3, RORγt and Foxp3, representing Th1, Th2, Th17 and Treg cells respectively. No study has directly determined the relative presence of each of these T cell subsets concomitantly in a model of allergic airway inflammation. In this study we determined the degree of expansion of these T cell subsets, in the lungs of allergen challenged mice. Cell proliferation was determined by incorporation of 5-bromo-2'-deoxyuridine (BrdU) together with 7-aminoactnomycin (7-AAD). The immunohistochemical localisation of T cells in the lung microenvironments was also quantified. Local expression of cytokines, chemokines and receptor genes was measured using real-time RT-PCR array analysis in tissue sections isolated by laser microdissection and pressure catapulting technology. Allergen exposure increased the numbers of T-bet(+), GATA-3(+), RORγt(+) and Foxp3(+) cells in CD4(+)CD25(+) and CD4(+)CD25(-) T cells, with the greatest expansion of GATA-3(+) cells. The majority of CD4(+)CD25(+) T-bet(+), GATA-3(+), RORγt(+) and Foxp3(+) cells had incorporated BrdU and underwent proliferation during allergen exposure. Allergen exposure led to the accumulation of T-bet(+), GATA-3(+) and Foxp3(+) cells in peribronchial and alveolar tissue, GATA-3(+) and Foxp3(+) cells in perivascular tissue, and RORγt(+) cells in alveolar tissue. A total of 28 cytokines, chemokines and receptor genes were altered more than 3 fold upon allergen exposure, with expression of half of the genes claimed in all three microenvironments. Our study shows that allergen exposure affects all T effector cells in lung, with a dominant of Th2 cells, but with different local cell distribution, probably due to a distinguished local inflammatory milieu.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Immunology in the medical area (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Lungmedicin och allergi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Respiratory Medicine and Allergy (hsv//eng)

Nyckelord

T cells

allergic inflammation

Flow Cytometry

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