Evidence that CD8+ dendritic cells enable the development of gammadelta T cells that modulate airway hyperresponsiveness.
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.
Department of Immunology, National Jewish Medical and Research Center, Denver, CO 80206, USA.
Laura
L
Cook
Nobuaki
N
Miyahara
Niyun
N
Jin
J M
JM
Wands
Christian
C
Taube
Christina L
CL
Roark
Terry A
TA
Potter
Erwin W
EW
Gelfand
Rebecca L
RL
O'Brien
Willi K
WK
Born
D000818:Animals; D016535:Bronchial Hyperreactivity / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D016827:CD8 Antigens / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000172:deficiency / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism
D016827:CD8 Antigens; D016692:Receptors, Antigen, T-Cell, gamma-delta