Induction Of Ts Cells Research Articles

Effect of N-(2-carboxyphenyl)-4-chloroanthranilic acid disodium salt (CCA) on the induction of helper and suppressor T cells in vitro and in vivo.

Keyhole lympet hemocyanin (KLH)-specific suppressor T (Ts) cells that suppress the in vitro secondary anti-trinitrophenyl (TNP) PFC response to TNP-KLH could be induced when murine spleen cells were precultured with KLH. N-(2-carboxyphenyl)-4-chloroanthranilic acid disodium salt (CCA) at 1-100 micrograms/ml augmented the in vitro induction of Ts cells when the cells were precultured with a suboptimal dose of KLH (10 micrograms/ml). Ts cell-induction was, however, rather slightly inhibited by the same concentrations of CCA when the lymphocytes were precultured with an optimal amount of KLH (100 micrograms/ml). In the in vivo experiments, the daily administration of 10 mg/kg CCA for 4 weeks augmented or inhibited Ts cell-induction when mice were immunized with a suboptimal (30 micrograms/body) or an optimal (100 micrograms/body) amount of KLH, respectively. However, CCA had no effect on the induction of Ts cells by concanavalin A in vivo. On the other hand, CCA augmented the induction of helper T (Th) cells both in vitro and in vivo when Th cells were induced with a suboptimal amount of antigens. In contrast, the augmentative effect was no longer observed when Th cells were induced by an optimal amount of antigens. These results suggest that CCA is a compound showing immunomodulating properties that affect Ts and Th cell-induction depending on immunological conditions. These immunopharmacological profiles are discussed in connection with its clinical application to an autoimmune disease like rheumatoid arthritis.

EFFECT OF N-(2-CARBOXYPHENYL)-4-CHLOROANTHRANILIC ACID DISODIUM SALT (CCA) ON THE INDUCTION OF HELPER AND SUPPRESSOR T CELLS IN VITRO AND IN VIVO

Keyhole lympet hemocyanin (KLH)-specific suppressor T (Ts) cells that suppress the in vitro secondary anti-trinitrophenyl (TNP) PFC response to TNP-KLH could be induced when murine spleen cells were precultured with KLH. N-(2-carboxy-phenyl)-4-chloroanthranilic acid disodium salt (CCA) at 1-100 μg/ml augmented the in vitro induction of Ts cells when the cells were precultured with a suboptimal dose of KLH (10 μg/ml). Ts cell-induction was, however, rather slightly inhibited by the same concentrations of CCA when the lymphocytes were precultured with an optimal amount of KLH (100 μg/ml). In the in vivo experiments, the daily administration of 10 mg/kg CCA for 4 weeks augmented or inhibited Ts cell-induction when mice were immunized with a suboptimal (30 μg/body) or an optimal (100 /μg/body) amount of KLH, respectively. However, CCA had no effect on the induction of Ts cells by concanavalin A in vivo. On the other hand, CCA augmented the induction of helper T (Th) cells both in vitro and in vivo when Th cells were induced with a suboptimal amount of antigens. In contrast, the augmentative effect was no longer observed when Th cells were induced by an optimal amount of antigens. These results suggest that CCA is a compound showing immunomodulating properties that affect Ts and Th cell-induction depending on immunological conditions. These immunopharmacological profiles are discussed in connection with its clinical application to an autoimmune disease like rheumatoid arthritis.

Modulation of Suppressor Mechanisms in Allergic Contact Dermatitis: 5. Evidence That Inhibition of Suppressor T Lymphocytes by Corynebacterium parvum Is Mediated by Interferon

Using a contact hypersensitivity model in BALB/c mice we have previously been able to show that Corynebacterium parvum or C. parvum serum (C.p.s.) of mice treated 24 hr before with C. parvum inhibited the suppressor T-lymphocyte (Ts-cell) response induced by epicutaneous antigen overload with 2,4-dinitrofluorobenzene (DNFB) or by i.v. injection of 2,4-dinitrobenzene sulfonic acid (DNBSO3) without inhibition of the T effector cell response (TDH-cell). In the present investigation we further analyzed the factor responsible for Ts-cell inhibition. Treatment of the C.p.s. with sheep-antimouse interferon (IFN) globulin neutralized its Ts-cell inhibitory effect. Intravenous (i.v.) injection of a crude mouse fibroblast IFN (340 U per mouse) 2 hr after i.v. application of a dose of DNBSO3 inducing tolerance had a similar Ts-cell inhibitory effect as observed with C.p.s. Injection of an electrophoretically pure alpha- and beta-IFN preparation (1000 U per mouse) increased contact sensitivity in mice sensitized with an antigen overload and inhibited the induction of Ts-cells by DNBSO3 i.v. This result is highly suggestive that the Ts-cell inhibitory factor in serum of C. parvum-treated mice is IFN and it shows that Ts-cells as compared to TDH-cells are susceptible to the inhibitory effect of highly purified IFN. This finding suggests that IFN may be an important immunoregulatory factor of delayed hypersensitivity not only in contact allergy but also in bacterial and viral defense.