| Abstract: |
During 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 FcγRIIb1 and 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 lack FcγRIII expression and could not mediate antibody-dependent cellular cytotoxicity through FcγRIII. |
| Keywords: |
controlled study; nonhuman; polymerase chain reaction; cd8 antigen; t lymphocyte; t-lymphocytes; animal cell; mouse; animals; mice; mice, knockout; interleukin 2; cell differentiation; mice, inbred c57bl; lymphocyte differentiation; t lymphocyte receptor; antibodies, monoclonal; molecular sequence data; immunoglobulin g; cell culture; thymus; thymus gland; messenger rna; natural killer cell; base sequence; fc receptor; receptors, igg; aging; fetus; cd4 antigen; organ culture techniques; thymocyte; receptors, antigen, t-cell, alpha-beta; fetus development; cell mediated cytotoxicity; ontogeny; receptors, antigen, t-cell, gamma-delta; lymphocyte subpopulation; receptors, ige; intestine epithelium; priority journal; article; antigens, t-independent; organ culture; fetal thymocyte; intestinal intraepithelial lymphocyte; large granular lymphocyte
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