T lymphocyte development in the absence of Fc epsilon receptor I gamma subunit: analysis of thymic-dependent and independent alpha beta and gamma delta pathways.
During fetal development, early thymocyte progenitors transiently express low affinity Fc receptors for IgG (Fc gamma R) of both Fc gamma RII and III isoforms. Only the Fc gamma RIII isoform requires association of an Fc gamma RIII (CD16) alpha subunit with an Fc epsilon RI gamma homodimer for surface expression. To address the role of Fc gamma R in ontogeny, we studied thymic development in Fc epsilon RI gamma-/- mice. We fine that day 14.5 CD4-CD8- double-negative (DN) fetal thymocytes of Fc epsilon RI gamma-/- mice express mRNA of both Fc gamma RIIb1 and Fc gamma RIII. Surface expression of Fc gamma RII/III is readily detected on these cells. It appears that Fc gamma RIIb1, whose surface expression is Fc epsilon RI gamma independent, replaces Fc gamma RIII 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 Fc epsilon RI gamma. However, alterations were noted in adult animals among the DN alpha beta TCR+ thymocytes and peripheral splenic DN T cells as well as CD8 alpha alpha + intestinal intraepithelial lymphocytes (iIEL). In contrast to conventional T lymphocytes, which do not express either Fc gamma RIII or Fc epsilon RI gamma, DN alpha beta TCR+ thymocytes and extrathymically derived alpha beta TCR+ and gamma delta TCR+ CD8 alpha alpha + beta- iIEL express TCR which incorporate Fc epsilon RI gamma 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 Fc epsilon RI gamma. Thus, we observed alterations in adult DN alpha beta TCR+ thymocytes, splenic DN alpha beta TCR+ and DN gamma delta TCR+ large granular lymphocytes (LGL), and alpha beta TCR+ and gamma delta TCR+ CD8 alpha alpha+beta- iIEL, but no detectable changes in their major fetal thymic developmental pathways. Cultivation of peripheral DN alpha beta TCR+ and DN gamma delta TCR+ cells from Fc epsilon RI gamma-/- mice with interleukin-2 generates LGL which mediate natural killer activity. Unlike LGL from wild-type C57BL/6 mice, LGL from Fc epsilon RI gamma-/- mice lack Fc gamma RIII expression and could not mediate antibody-dependent cellular cytotoxicity through Fc gamma RIII.
Heiken
H
H
Dana-Farber Cancer Institute, Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
Schulz
R J
RJ
Ravetch
J V
JV
Reinherz
E L
EL
Koyasu
S
S
D000375:Aging; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000955:Antigens, T-Independent / Q000276:immunology; D001483:Base Sequence; D002454:Cell Differentiation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009924:Organ Culture Techniques; D016133:Polymerase Chain Reaction; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis / Q000502:physiology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis / Q000502:physiology*; D017455:Receptors, IgE / Q000172:deficiency* / Q000276:immunology; D017452:Receptors, IgG / Q000172:deficiency* / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D000955:Antigens, T-Independent; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D017455:Receptors, IgE; D017452:Receptors, IgG