Interaction between cytokines and 8-mercaptoguanosine in humoral immunity: synergy with interferon.
In previous studies it has been demonstrated that a T cell-like differentiation signal is transmitted by C8-substituted guanine ribonucleosides such as 8-mercaptoguanosine (8MGuo) to antigen-stimulated B cells. A large subset of potentially reactive B cells remains unresponsive to antigen even in the presence of signals provided by these nucleosides except when this signal is preceded by a soluble activity present in mixed lymphocyte culture supernatants. Studies with purified preparations of interleukin (IL)-1, IL-2, IL-3, granulocyte-macrophage colony stimulating factor, B cell stimulatory factor 1 (IL-4), and B cell growth factor II (IL-5) indicated that none of these activities is capable of synergizing with 8MGuo to augment B cell responsiveness to antigen. Therefore, supernatants from a number of cloned cell lines were examined for activity that could synergize with 8MGuo, in order to determine the cellular source of this activity. Soluble products secreted by cloned 24/G1 T cells act synergistically with 8MGuo to evoke enhanced antibody responses to specific antigen in populations of purified B cells. Because concanavalin (Con) A-activated 24/G1 cells produce large quantities of interferon-gamma (IFN-gamma), the possibility that interferons might mediate synergy with 8MGuo was investigated. Purified murine IFN-gamma is unable to interact synergistically with 8MGuo; moreover, treatment of active 24/G1 supernatants with monoclonal anti-IFN-gamma antibodies or at pH 2 fails to abrogate their ability to synergize. In contrast to IFN-gamma, when B cells were supplemented with either IFN-alpha or IFN-beta, antigen-dependent synergy with 8MGuo was observed. However, abrogation of IFN-alpha and IFN-beta activity with specific antibodies fails to interfere with synergy between 8MGuo and mixed lymphocyte culture or Con A supernatants. Therefore, it appears that although IFN-alpha and IFN-beta are not responsible for the synergizing activity present in activated T cell supernatants, they nonetheless represent a previously unrecognized source of synergizing activity.
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects*; D001688:Biological Products / Q000494:pharmacology*; D003115:Colony-Stimulating Factors / Q000494:pharmacology; D016207:Cytokines; D004357:Drug Synergism; D006133:Growth Substances / Q000494:pharmacology; D006151:Guanosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D007370:Interferon Type I / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D007377:Interleukin-3 / Q000494:pharmacology; D015847:Interleukin-4; D008222:Lymphokines / Q000494:pharmacology; D051379:Mice; D013601:T-Lymphocytes / Q000502:physiology; D013872:Thionucleosides / Q000494:pharmacology*
D001688:Biological Products; D003115:Colony-Stimulating Factors; D016207:Cytokines; D006133:Growth Substances; D007370:Interferon Type I; D007375:Interleukin-1; D007376:Interleukin-2; D007377:Interleukin-3; D008222:Lymphokines; D013872:Thionucleosides; D006151:Guanosine; D015847:Interleukin-4; D007371:Interferon-gamma; C037031:8-thioguanosine