Aging of the murine immune system is reflected by declining ability to generate antibodies that promote elimination of Trypanosoma musculi.

Trypanosoma musculi established extracellular infections in aged BC3F1 and C57BL/6 mice that were approximately 10 times greater and twice as long in duration as those in young adult mice. Elimination of T. musculi infections was found to be an antibody-dependent, cell-mediated process involving effector (presumably phagocytic) cells in the liver and, to a lesser extent, the spleen. A major difference between young and aged mice of the C57BL/6 strain was the deficiency in the ability of aged animals to generate antibodies of appropriate specificity and/or isotype in sufficient amount to promote trypanosome elimination. Indeed, at the time when infected young-adult mice began to produce antibodies that facilitated rapid trypanosome clearance (in young adult, but not in aged animals), the serum of aged mice was found to contain substances that inhibited parasite clearance. Overall, however, the development of antibodies of different isotypes, capable of reacting with intact trypanosomes, was about the same in young and aged animals. Hepatic and splenic effector cells of old mice were at least as efficient as those of young adults. The immunoblotting procedure was used to try to detect trypanosome Ag against which aged animals failed to generate antibodies of one or more isotypes. The complexity of the reactions of infected mouse serum antibodies with the spectrum of trypanosome Ag precluded a precise analysis. However, it was apparent that a delay in the appearance of antibodies of IgG2a and IgG2b isotypes, against Ag of relatively high m.w., was typical of aged, in comparison to young, mice. More exacting analyses, involving fractionated trypanosome extracts and mAb of varying isotypes, are underway to identify key trypanosome Ag that elicit antibodies of isotypes that can facilitate hepatic and splenic clearance of the parasites. This line of investigation will provide information that, in addition to its intrinsic interest, may be vital in judging the future impact of endemic parasitic infections on the emerging cohort of elderly persons in developing tropical nations.