Evidence That Cd8+ Dendritic Cells Enable the Development of T Cells That Modulate Airway Hyperresponsiveness

Cook, L.; Miyahara, N.; Jin, N.; Wands, J.M.; Taube, C.; Roark, C.L.; Potter, T.A.; Gelfand, E.W.; O'Brien, R.L.; Born, W.K.

The Journal of Immunology 181(1): 309-319


DOI: 10.4049/jimmunol.181.1.309
Accession: 068491040

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Airway hyperresponsiveness (AHR), a hallmark of asthma and several other diseases, can be modulated by gammadelta T cells. In mice sensitized and challenged with OVA, AHR depends on allergen-specific alphabeta T cells; but Vgamma1+ gammadelta T cells spontaneously enhance AHR, whereas Vgamma4+ gammadelta T cells, after being induced by airway challenge, suppress AHR. The activity of these gammadelta T cell modulators is allergen nonspecific, and how they develop is unclear. We now show that CD8 is essential for the development of both the AHR suppressor and enhancer gammadelta T cells, although neither type needs to express CD8 itself. Both cell types encounter CD8-expressing non-T cells in the spleen, and their functional development in an otherwise CD8-negative environment can be restored with transferred spleen cell preparations containing CD8+ dendritic cells (DCs), but not CD8+ T cells or CD8- DCs. Our findings suggest that CD8+ DCs in the lymphoid tissues enable an early step in the development of gammadelta T cells through direct cell contact. DC-expressed CD8 might take part in this interaction.