TY - JOUR
T1 - Influence of retinoic acid on the differentiation pathway of T cells in the thymus
AU - Yagi, Junji
AU - Uchida, Takafumi
AU - Kuroda, Kotaro
AU - Uchiyama, Takehiko
N1 - Funding Information:
We are grateful to Dr. T. Tadakuma, Dr. G. Suzuki, Dr. T. Naka-yama and Dr. O. Kanagawa for monoclonal antibodies, and to K. Futatuyama and Dr. U. Hayasaka for help in 3-color ¯ow cytometry. We want to thank Naoko Ohnishi for technical help. This work was supported in part by grants from the Ministry of Education, Science, Sports, and Culture of Japan and the Ministry of Public Welfare of Japan.
PY - 1997/11/1
Y1 - 1997/11/1
N2 - 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 (CD3(high) 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 α but not β and γ 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 Vβ3(high) cells was greatly reduced (1.4% of the CD3(high) cells) in response to the mouse mammary tumor virus-6-encoded superantigen, but Vβ3-bearing cells were rescued from the deletion in the presence of all-trans-RA (5.6% of the CD3(high) 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.
AB - 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 (CD3(high) 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 α but not β and γ 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 Vβ3(high) cells was greatly reduced (1.4% of the CD3(high) cells) in response to the mouse mammary tumor virus-6-encoded superantigen, but Vβ3-bearing cells were rescued from the deletion in the presence of all-trans-RA (5.6% of the CD3(high) 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.
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U2 - 10.1006/cimm.1997.1203
DO - 10.1006/cimm.1997.1203
M3 - Article
C2 - 9398402
AN - SCOPUS:17944390126
VL - 181
SP - 153
EP - 162
JO - Cellular Immunology
JF - Cellular Immunology
SN - 0008-8749
IS - 2
ER -