Mechanisms in opposite modulation of spleen cell and lymph node cell responses to mitogens following muramyl dipeptide treatment in vivo.
It has been reported that a muramyl dipeptide (MDP) treatment regimen (200 micrograms MDP per mouse, Days -4, -3, -2, and -1) that, given prophylactically, affords protection against several infectious agents also induces lymph node hyperplasia, lymph node cell (LNC) hyperresponsiveness to mitogens, and spleen cell hyporesponsiveness to mitogens. The purpose of the present work was to extend those studies and delineate cellular mechanisms involved in these phenomena. It has been found that hyperresponsiveness of LNC was prolonged (7 days) posttreatment; in contrast, hyporesponsiveness of spleen cells was transient and rebounded by Day 4 posttreatment. Hyperresponsiveness of LNC and hyporesponsiveness of spleen cells actively enhanced and depressed normal lymphoid cell responses, respectively, in cell mixing experiments. Hyporesponsiveness of spleen cells was associated with the plastic-nonadherent, non-B-cell fraction and nylon wool-nonadherent subpopulations. Indomethacin (10(-6) M) did not abrogate hyporesponsiveness of spleen cells. These data suggest that splenic suppressor T cells result from MDP treatment and were responsible for spleen cell hyporesponsiveness. On the other hand, hyperresponsiveness of LNC was associated with the nylon wool-adherent cell subpopulations and a higher percentage of nonspecific esterase-positive cells. Hyporesponsiveness of spleen cells was associated with deficient production of interleukin 2 (IL-2), but not of interleukin 1 (IL-1). In contrast, hyperresponsiveness of LNC was not explained by enhanced IL-1 or IL-2 production.
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000494:pharmacology*; D000818:Animals; D002448:Cell Adhesion; D008198:Lymph Nodes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008934:Mitogens / Q000494:pharmacology*; D013154:Spleen / Q000166:cytology / Q000187:drug effects* / Q000276:immunology
D008934:Mitogens; D000119:Acetylmuramyl-Alanyl-Isoglutamine