T(h)1/T(h)2 cell differentiation of developing CD4 single-positive thymocytes.
In this study we investigate the stage at which developing T cells in the thymus acquire the ability to differentiate into T(h)1 and T(h)2 cells. We addressed this question by using sorted heat-stable antigen (HSA)(+) and HSA(-) CD4 single-positive (SP) thymocytes prepared from ovalbumin-specific TCRalphabeta transgenic mice and an in vitro T(h)1/T(h)2 differentiation culture system. HSA(-) CD4 SP thymocytes show nearly full functional capacity to differentiate into either T(h)1 or T(h)2 cells. A dramatic difference was observed, however, between HSA(+) and HSA(-) CD4 SP thymocytes in the efficiency for T(h)1 cell differentiation. TCR function of HSA(+) CD4 SP thymocytes appeared to be fully developed because antigen-induced proliferation and IL-2 production were essentially equivalent to that of HSA(-) CD4 SP thymocytes. However, the levels in IL-12 receptor (IL-12R) beta2 chain expression following anti-TCR stimulation were dramatically low in the HSA(+) CD4 SP thymocytes. Decreased IL-12-induced STAT4 phosphorylation was also observed. Moreover, IL-12-dependent transcriptional up-regulation of T-bet and STAT4 was deficient in the HSA(+) CD4 SP thymocytes. Thus, the poor capacity of HSA(+) CD4 SP thymocytes to proceed to T(h)1 cell differentiation appears to be at least partly due to underdeveloped capacity in IL-12R expression and function.
Kikkawa
Emiko
E
Department of Molecular Immunology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
Yamashita
Masakatsu
M
Kimura
Motoko
M
Omori
Miyuki
M
Sugaya
Kaoru
K
Shimizu
Chiori
C
Katsumoto
Takuo
T
Ikekita
Masahiko
M
Taniguchi
Masaru
M
Nakayama
Toshinori
T
D000818:Animals; D000941:Antigens / Q000008:administration & dosage; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D015704:CD4 Antigens / Q000378:metabolism; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000378:metabolism; D066298:In Vitro Techniques; D018664:Interleukin-12 / Q000494:pharmacology; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000378:metabolism; D018123:Receptors, Interleukin / Q000378:metabolism; D053707:Receptors, Interleukin-12; D050797:STAT4 Transcription Factor; D020825:T-Box Domain Proteins; D018417:Th1 Cells / Q000166:cytology* / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000166:cytology* / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D000098815:T-bet Transcription Factor
D000941:Antigens; D000945:Antigens, Differentiation, T-Lymphocyte; D015704:CD4 Antigens; D004268:DNA-Binding Proteins; C508443:Il12rb2 protein, mouse; D007376:Interleukin-2; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018123:Receptors, Interleukin; D053707:Receptors, Interleukin-12; D050797:STAT4 Transcription Factor; C494091:Stat4 protein, mouse; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D015534:Trans-Activators; D014157:Transcription Factors; D018664:Interleukin-12; D010047:Ovalbumin