Regulation of T-cell activation and T-cell growth factor (TCGF) production by hydrogen peroxide.
Activated macrophages are known to release a variety of immunoregulatory substances including the low-molecular-weight substances hydrogen peroxide and lactate. We report here that lactate but not hydrogen peroxide is capable of supporting a substantial production of T-cell growth factor (TCGF) in cultures of accessory cell-depleted splenic T-cell populations after stimulation with concanavalin A. Hydrogen peroxide and its biosynthetic precursor superoxide anion (O2-) mediate, however, a strong augmentation of the TCGF production by accessory cell-depleted T-cell populations in the presence of lactate. Lactate inhibits the incorporation of [3H]thymidine in short-term cultures (18-26 hr) of accessory cell-depleted T cells. This confirms the rule that (optimal) production of T-cell growth factor requires a growth inhibitory signal. Concentrations of hydrogen peroxide which augment TCGF production most effectively (i.e., 1 X 10(-5) M) do not inhibit the incorporation of [3H]thymidine; and higher concentrations (3 X 10(-5)-1 X 10(-4) M) of hydrogen peroxide inhibit both the production of TCGF and the incorporation of [3H]thymidine. In agreement with the augmenting effect of hydrogen peroxide on TCGF production, it was observed that the proliferative response in mixed lymphocyte cultures is suppressed by catalase and augmented by 1 X 10(-5) M H2O2. Proliferative and cytotoxic responses in mixed lymphocyte cultures with an external source of interleukin 2 (IL-2) in contrast, are not augmented by 1 X 10(-5) M H2O2. The relatively high concentration of 1 X 10(-4) M hydrogen peroxide was found to inhibit the proliferative responses in mixed lymphocyte cultures with or without external IL-2 but not the cytotoxic response in the presence of IL-2. This indicates that CTL precursor cells may be relatively resistant against H2O2.
D000818:Animals; D000938:Antigen-Presenting Cells / Q000502:physiology; D003208:Concanavalin A / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic; D004247:DNA / Q000096:biosynthesis; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D007111:Immunity, Cellular; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000096:biosynthesis*; D008213:Lymphocyte Activation / Q000187:drug effects*; D007959:Lymphocyte Culture Test, Mixed; D008262:Macrophage Activation; D008264:Macrophages / Q000502:physiology*; D051379:Mice; D013481:Superoxides / Q000494:pharmacology; D013601:T-Lymphocytes / Q000502:physiology*
D007376:Interleukin-2; D003208:Concanavalin A; D013481:Superoxides; D004247:DNA; D006861:Hydrogen Peroxide