Differentiation of Human T Cells Alters Their Repertoire of G Protein α-Subunits

Because T cell differentiation leads to an expanded repertoire of chemokine receptors, a subgroup of G protein-coupled receptors, we hypothesized that the repertoire of G proteins might be altered in parallel. We analyzed the abundance of mRNA and/or protein of six G protein alpha-subunits in human CD4(+) and CD8(+) T cell subsets from blood. Although most G protein alpha-subunits were similarly expressed in all subsets, the abundance of G alpha(o), a protein not previously described in hematopoietic cells, was much higher in memory versus naive cells. Consistent with these data, activation of naive CD4(+) T cells in vitro significantly increased the abundance of G alpha(o) in cells stimulated under nonpolarizing or T(H)17 (but not T(H)1 or T(H)2)-polarizing conditions. In functional studies, the use of a chimeric G protein alpha-subunit, G alpha(qo5), demonstrated that chemokine receptors could couple to G alpha(o)-containing G proteins. We also found that G alpha(i1), another alpha-subunit not described previously in leukocytes, was expressed in naive T cells but virtually absent from memory subsets. Corresponding to their patterns of expression, siRNA-mediated knockdown of G alpha(o) in memory (but not naive) and G alpha(i1) in naive (but not memory) CD4(+) T cells inhibited chemokine-dependent migration. Moreover, although even in G alpha(o)- and G alpha(i1)-expressing cells mRNAs of these alpha-subunits were much less abundant than G alpha(i2) or G alpha(i3), knockdown of any of these subunits impaired chemokine receptor-mediated migration similarly. Together, our data reveal a change in the repertoire of G alpha(i/o) subunits during T cell differentiation and suggest functional equivalence among G alpha(i/o) subunits irrespective of their relative abundance.