Requirement of the Fc receptor common γ-chain for γδ T cell-mediated promotion of murine experimental autoimmune encephalomyelitis

Immunoglobulin Fc gamma receptors (Fc gamma R) are comprised of a ligand-binding alpha-chain that sometimes associates with a cell signaling common gamma-chain. These receptors comprise an important family of effector molecules that link humoral and cell-mediated adaptive immunity and regulate innate immunity. Recent animal studies suggest that Fc gamma R in general, and FcR alpha-chains in particular, are required for full development of experimental autoimmune encephalomyelitis (EAE). We show here that deletion of the gamma-chain renders mice resistant to EAE, whereas deletion of the alpha-chains of Fc gamma RI, Fc gamma RIIB and Fc gamma RIII has no protective effect. Susceptibility to EAE is fully restored in common gamma-chain(-/-) mice into which wild-type splenocytes are adoptively transferred, but EAE is not restored in common gamma-chain(-/-) mice given wild-type splenocytes depleted of 76 T cells. These data indicate that although the common gamma-chain is required for full development of EAE in mice, this requirement is likely Fc gamma R alpha-chain-independent. Expression of the common gamma-chain by gamma delta T cells, probably in conjunction with the T cell receptor/CD3 complex, is likely the key requirement for full development of EAE.