Analysis of the T-cell receptor (TCR) repertoire of innate CD4+ T cells selected by major histocompatibility complex (MHC) class II-dependent thymocyte-thymocyte (T-T) interaction (T-T CD4+ T cells) is essential for predicting the characteristics of the antigens that bind to these T cells and for distinguishing T-T CD4+ T cells from other types of innate T cells. Using the TCRmini Tg mouse model, we show that the repertoire of TCRalpha chains in T-T CD4+ T cells was extremely diverse, in contrast to the repertoires previously described for other types of innate T cells. The TCRalpha chain sequences significantly overlapped between T-T CD4+ T cells and conventional CD4+ T cells in the thymus and spleen. However, the diversity of the TCRalpha repertoire of T-T CD4+ T cells seemed to be restricted compared with that of conventional CD4+ T cells. Interestingly, the frequency of the parental OT-II TCRalpha chains was significantly reduced in the process of T-T interaction. This diverse and shifted repertoire in T-T CD4+ T cells has biological relevance in terms of defense against diverse pathogens and a possible regulatory role during peripheral T-T interaction.
Amino Acid Sequence ; Animals ; Antigens, Surface/metabolism ; CD4-Positive T-Lymphocytes/cytology/*immunology/*metabolism ; Cell Communication ; Cell Differentiation/genetics/immunology ; Clonal Evolution ; Histocompatibility Antigens Class II/*immunology ; *Immunity, Innate ; Immunophenotyping ; Lymphocyte Count ; Mice ; Mice, Knockout ; Mice, Transgenic ; Peptide Fragments/chemistry ; Phenotype ; Receptors, Antigen, T-Cell/chemistry/*genetics/metabolism ; Receptors, Antigen, T-Cell, alpha-beta/chemistry/genetics ; Spleen/cytology ; Thymocytes/cytology/immunology/metabolism

BACKGROUNDCryptotanshinone (CT) is the major active constituent of Salvia miltiorrhiza Bunge. The present study was carried out to investigate the effects of CT on rats with adjuvant arthritis (AA).

METHODSAA was induced by the metatarsal footpad injection with complete Freund's adjuvant in male Sprague-Dawley rats. The secondary inflammatory reaction was evaluated by hind paw swelling and the polyarthritis index. Activity of interleukin-1 (IL-1) was detected by the concanavalin A-induced thymocytes proliferation assay. The lymphocytes proliferation and IL-2 production were assayed by 3-(4,5-2dimethylthiazal-2yl)2,5-diphenyltetrazoliumbromide (MTT) and activated mouse splenocytes proliferation, respectively.

RESULTSIntragastric administration of CT (50 and 100 mg/kg) significantly decreased secondary inflammatory reactions and increased the spleen and thymus index. There was a marked immunologic and inflammatory response in the AA model, which was accompanied by the decrease of thymocyte proliferation and IL-2 production as well as the increase of IL-1 production. CT apparently enhanced thymocyte proliferation and decreased IL-1 production in AA rats.

CONCLUSIONThese results indicate that CT may exert its anti-inflammatory and immunoregulatory effects through inhibiting lymphocyte proliferation and production of pro-inflammatory mediators.

Animals ; Arthritis, Experimental ; drug therapy ; immunology ; metabolism ; Cell Proliferation ; drug effects ; Interleukin-1 ; metabolism ; Interleukin-2 ; metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Phenanthrenes ; therapeutic use ; Rats ; Rats, Sprague-Dawley ; Thymocytes ; cytology ; drug effects ; metabolism