Influence of retinoic acid on the differentiation pathway of T cells in the thymus.
This study investigated the ability of retinoic acid (RA) to influence T cell differentiation. All-trans-RA had marked effects on T cell differentiation in murine fetal thymic organ cultures (FTOCs). The time course of the effect of all-trans-RA in FTOC of day 14 C57BL/6 embryos revealed a twofold increase in the frequency of CD4 single-positive (SP) cells and a high level of CD3-bearing cells (CD3high cells) at a later stage of T cell development. At an earlier stage, all-trans-RA induced a twofold increase in the frequency of CD4 SP cells, but significantly suppressed the upregulation of CD3 and TCR. Reverse transcription-PCR using RA receptor (RAR) subtype-specific primers showed that RAR alpha but not beta and gamma is expressed during T cell development in the thymus and that its expression was associated with the generation of CD4/CD8 double-positive (DP) cells. In FTOC of day 16 BALB/c embryos, the level of V beta 3high cells was greatly reduced (1.4% of the CD3high cells) in response to the mouse mammary tumor virus-6-encoded superantigen, but V beta 3-bearing cells were rescued from the deletion in the presence of all-trans-RA (5.6% of the CD3high cells). Further, the inhibitory effect of all-trans-RA on thymocyte deletion was observed when the deletion was induced by a low concentration of staphylococcal enterotoxin B in FTOC. Taken together, these data suggest that RA increases the frequency of mature and self-reactive T cells in the thymus, possibly by inhibiting the process of negative selection at the DP stage of T cell differentiation.
Yagi
J
J
Department of Microbiology and Immunology, Tokyo Women's Medical College, Japan.
Uchida
T
T
Kuroda
K
K
Uchiyama
T
T
D000818:Animals; D000956:Antigens, Viral / Q000096:biosynthesis / Q000235:genetics; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D017637:Clonal Deletion / Q000187:drug effects; D004768:Enterotoxins / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009924:Organ Culture Techniques; D018089:Superantigens / Q000096:biosynthesis / Q000235:genetics; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects*; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects*; D014212:Tretinoin / Q000494:pharmacology*
D000956:Antigens, Viral; D004768:Enterotoxins; D018089:Superantigens; C031818:enterotoxin B, staphylococcal; D014212:Tretinoin