title: Dextran augments delayed-type hypersensitivity by interrupting one limb of the suppressor cascade.
abstract: We have studied the immunomodulatory effect of dextran on the development of delayed-type contact hypersensitivity to a hapten in mice. Administration of an optimal dose of dextran 2 hours before applying picryl chloride to abdominal skin caused a twofold rise in the level of hapten-specific DTH. A study of the kinetics of development of DTH under the influence of dextran showed that comparable levels of response could be seen 2 days earlier in treated than in untreated mice, i.e., on the third day in contrast to the fifth day after sensitization. The peak of the responses, while greater in dextran-treated mice than in normal controls, remained the same at 5 days. Adoptive transfer studies revealed that comparable levels of DTH were conferred upon recipient mice by half the number of splenic cells from dextran-treated mice than that required from normal sensitized mice. Because several suppressor mechanisms are known to down-regulate DTH, we have studied dextran's effect on the neutralization of these systems as a possible explanation for its enhancing capabilities. Detailed examination was made of dextran's effect on the two suppressor T cells, Ts1 and Ts3, that act in tandem as well as its effect on the Ts1 and macrophage that work in combination. Both systems depress the efferent limb of DTH. We have found that dextran blocks the Ts1-macrophage pathway that controls DTH. Ts1 was found to arise normally in mice pretreated with dextran. Furthermore, Ts1 from dextran-treated mice produced TsF1 normally. However, we have found that dextran interferes with the production of macrophage suppressor factor (M phi-SF). Interference was partial when dextran was introduced during the interval in which macrophages were being armed with TsF1, and it was complete when dextran was put with pre-armed macrophages before they were triggered with antigen for production of M phi-SF. On the other hand, the Ts1-Ts3 limb of suppression remained unaffected by exposure to the immunomodulator. We found Ts3 arose normally in hapten-sensitized mice that had been pretreated with dextran. In addition, Ts3 became armed with TsF1 in vitro in the presence of dextran since the cells functioned properly to suppress mature DTH effector cells. Finally, TsF3 was able to act in vitro upon DTH effector cells despite the presence of dextran.(ABSTRACT TRUNCATED AT 400 WORDS)
authors.forename: J R
authors.initials: JR
authors.lastname: Battisto
authors.forename: K
authors.initials: K
authors.lastname: Beckman
authors.forename: B
authors.initials: B
authors.lastname: Yen-Lieberman
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D003911:Dextrans / Q000494:pharmacology*; D006241:Haptens / Q000276:immunology; D006968:Hypersensitivity, Delayed / Q000276:immunology*; D007108:Immune Tolerance; D007116:Immunization, Passive; D008213:Lymphocyte Activation / Q000187:drug effects; D008222:Lymphokines / Q000502:physiology; D008263:Macrophage Migration-Inhibitory Factors / Q000096:biosynthesis / Q000502:physiology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D010853:Picryl Chloride / Q000276:immunology; D013491:Suppressor Factors, Immunologic; D050378:T-Lymphocytes, Regulatory / Q000145:classification / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D003911:Dextrans; D006241:Haptens; D008222:Lymphokines; D008263:Macrophage Migration-Inhibitory Factors; D013491:Suppressor Factors, Immunologic; D010853:Picryl Chloride