Systematic development of distinct T cell receptor-gamma delta T cell subsets during fetal ontogeny.
To elucidate the developmental pattern and diversity of murine cluster of differentiation (CD)3-associated TCR-gamma delta heterodimers, adult and fetal thymocytes were examined for cell-surface expression of various gamma- and delta-encoded TCR. Biochemical analysis, using antisera specific for distinct C gamma gene products, revealed the presence of T cells expressing C gamma 1 and/or C gamma 4 heterodimers in adult and fetal CD4- CD8- thymocyte populations. Although CD4-CD8- thymocyte populations express both C gamma 1 and C gamma 4 TCR-gamma delta heterodimers early in fetal thymus development, the relative level of C gamma 4-expressing T cells was significantly lower than previously observed in peripheral lymphoid organs. In addition, biochemical studies revealed the presence of TCR-gamma delta heterodimer(s) expressed during fetal ontogeny which were not detected in adult thymocyte or peripheral lymphoid populations. Studies of N-glycosylation patterns of one of these heterodimers suggested that it contained a rearranged V gamma 3/C gamma 1 gene product. To examine in detail individual TCR-gamma delta heterodimers, a panel of TCR-gamma delta expressing hybridomas was prepared. Biochemical analysis at the clonal level revealed that indeed three distinct TCR-gamma delta heterodimers were present at day 16 of fetal thymus development, with TCR-gamma-chains most likely encoded by V gamma 2/C gamma 1, V gamma 3/C gamma 1, and V gamma/C gamma 4. Together these findings suggest an ordered development of TCR-gamma delta T cells in the thymus and selective expression of distinct TCR-gamma delta subsets in peripheral lymphoid organs such as spleen and lymph nodes.
Houlden
B A
BA
University of Chicago, Ben May Institute, IL 60637.
Cron
R Q
RQ
Coligan
J E
JE
Bluestone
J A
JA
D000375:Aging; D000818:Animals; D005314:Embryonic and Fetal Development; D014644:Genetic Variation; D006825:Hybridomas / Q000378:metabolism; D046911:Macromolecular Substances; D051379:Mice; D008810:Mice, Inbred C57BL; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D013601:T-Lymphocytes / Q000145:classification* / Q000378:metabolism / Q000502:physiology; D013950:Thymus Gland / Q000254:growth & development / Q000378:metabolism
D046911:Macromolecular Substances; D011948:Receptors, Antigen, T-Cell