Human lymphocytes bearing T cell receptor γ/δ are phenotypically diverse and evenly distributed throughout the lymphoid system

A direct quantitative and phenotypic cytofluorographic analysis of TCR-γ/δ⁺ lymphocytes as well as an immunohistologic study of their tissue distribution and microanatomy was made possible by the availability of two mAbs (anti-TCR-δ1 and anti-CγM1) specific for framework determinants on human TCR γ and δ chains, respectively. TCR-γ/δ⁺ lymphocytes, ranging between >0.5 and 16% of CD3⁺ cells, were found in fetal and postnatal thymus, fetal and adult peripheral lymphoid organs, and adult peripheral blood. While TCR-γ/δ⁺ lymphocytes comprised a small subpopulation of T cells (mean, ~4%) occasionally >10-16% of CD3⁺ cells expressed TCR-γ/δ. Virtually all TCR-γ/δ⁺ thymocytes/lymphocytes expressed CD7, CD2, and CD5 but were heterogeneous with respect to their expression of CD1, CD4, CD8, CD28, CD11b, CD16, and Leu-7. Human TCR-γ/δ⁺ cells populate both organized lymphoid tissues (thymus, tonsil, lymphnode, and spleen) as well as the gut- and skin-associated lymphoid systems at similar frequencies without obvious tropism for epithelial microenvironments. TCR-γ/δ⁺ lymphocytes tend to be located within a given organ wherever TCR-α/β⁺ lymphocytes are found. This study shows that TCR-γ/δ⁺ lymphocytes constitute a small but numerically important, phenotypically diverse T cell population distributed throughout the body. These results support the concept that TCR-γ/δ⁺ cells comprise a distinct, functionally heterogeneous, mature T cell sublineage that may substantially broaden the T cell repertoire at all immunologically relevant sites.