Evidence That CD8+ Dendritic Cells Enable the Development of γδ T Cells That Modulate Airway Hyperresponsiveness

• Published in: The Journal of immunology (1950) 2008-07, Vol.181 (1), p.309-319
• Main Authors: Cook, Laura, Miyahara, Nobuaki, Jin, Niyun, Wands, J. M., Taube, Christian, Roark, Christina L., Potter, Terry A., Gelfand, Erwin W., O'Brien, Rebecca L., Born, Willi K.
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.181.1.309

Airway hyperresponsiveness (AHR), a hallmark of asthma and several other diseases, can be modulated by γδ T cells. In mice sensitized and challenged with OVA, AHR depends on allergen-specific αβ T cells; but Vγ1+ γδ T cells spontaneously enhance AHR, whereas Vγ4+ γδ T cells, after being induced by airway challenge, suppress AHR. The activity of these γδ 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 γδ 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 γδ T cells through direct cell contact. DC-expressed CD8 might take part in this interaction.