Blood γδ T cells and γδ TCR V gene specificities in a single missense mutation (L→Q271) in the common gamma chain gene

The numbers of blood CD4⁺, CD8⁺, and CD4^- CD8^- T cells bearing αβ T-cell receptor (TCR) or γδ TCR molecules in males with a single missense mutation (L→Q271) in the common gamma chain gene (γ_c) were investigated by flow cytometry. Virtually all XCID^L→Q271 blood T cells that were CD4⁺ or CD8⁺ displayed αβ TCR but no γδ TCR. In contrast, CD4^- CD8^- T cells from affected males usually displayed γδ TCR, but no αβ TCR. The γδ TCR specificities were also studied. Except for the oldest subject, there was a direct relationship between blood CD3⁺ T cells that displayed γδ TCR and Vγ9 and Vδ2a specificities. Relative frequencies of CD3⁺ blood T cells that were Vγ9⁺ or Vδ2a⁺ were inversely related to age. In the oldest patient, the only detected γδ TCR specificity was Vδ1. Thus, in contrast to mice with no γ_c, XCID^L→Q271 blood T cells that bear γδ TCR with Vγ9/Vδ2a specificities develop but then decline in late childhood and thereafter. TCR with the Vδ1 specificity then appear in older survivors with XCID^L→Q271.