T lymphocyte development in the absence of Fcϵ receptor Iγ subunit: analysis of thymic‐dependent and independent αβ and γδ pathways

摘要

AbstractDuring fetal development, early thymocyte progenitors transiently express low affinity Fc receptors for IgG (FcγR) of both FcγRII and III isoforms. Only the FcγRIII isoform requires association of an FcγRIII (CD16) α subunit with an FcϵRIγ homodimer for surface expression. To address the role of FcγR in ontogeny, we studied thymic development in FcϵRIγ−/−mice. We find that day 14.5 CD4−CD8−double‐negative (DN) fetal thymocytes of FcϵRIγ−/−mice express mRNA of both FcγRIIb1and FcγRIII. Surface expression of FcγRII/III is readily detected on these cells. It appears that FcγRIIb1, whose surface expression is FcϵRIγ independent, replaces FcγRIII during thymic development in these animals. Moreover, subsequent development into CD4+CD8+double‐positive and CD4+CD8−and CD4−CD8+single‐positive subsets appears normal even in the absence of FcϵRIγ. However, alterations were noted in adult animals among the DN αβ TCR+thymocytes and peripheral splenic DN T cells as well as CD8αα+intestinal intraepithelial lymphocytes (iIEL). In contrast to conventional T lymphocytes, which do not express either FcγRIII or FcϵRIγ, DN αβ TCR+thymocytes and extrathymically derived αβ TCR+and γδ TCR+CD8αα+β−iIEL express TCR which incorporate FcϵRIγ as one of their subunits. Consistent with this, the TCR levels of these cells are lower than the TCR levels on cells from wild‐type C57BL/6 mice. Despite the reduction in the level of surface TCR, the development of these cells was unaltered by the absence of FcϵRIγ. Thus, we observed alterations in adult DN αβ TCR+thymocytes, splenic DN αβ TCR+and DN γδ TCR+large granular lymphocytes (LGL), and αβ TCR+and γδ TCR+CD8αα+β−iIEL, but no detectable changes in their major fetal thymic developmental pathways. Cultivation of peripheral DN αβ TCR+and DN γδ TCR+cells from FcϵRIγ−/−mice with interleukin‐2 generates LGL which mediate natural killer activity. Unlike LGL from wild‐type C57BL/6 mice, LGL from FcϵRIγ−/−mice l