Differentiation of human T cells alters their repertoire of G protein alpha-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 α-subunits in human CD4(+) and CD8(+) T cell subsets from blood. Although most G protein α-subunits were similarly expressed in all subsets, the abundance of Gα(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 Gα(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 α-subunit, Gα(qo5), demonstrated that chemokine receptors could couple to Gα(o)-containing G proteins. We also found that Gα(i1), another α-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 Gα(o) in memory (but not naive) and Gα(i1) in naive (but not memory) CD4(+) T cells inhibited chemokine-dependent migration. Moreover, although even in Gα(o)- and Gα(i1)-expressing cells mRNAs of these α-subunits were much less abundant than Gα(i2) or Gα(i3), knockdown of any of these subunits impaired chemokine receptor-mediated migration similarly. Together, our data reveal a change in the repertoire of Gα(i/o) subunits during T cell differentiation and suggest functional equivalence among Gα(i/o) subunits irrespective of their relative abundance.