CHANGES IN THE SUBSETS OF CD4-CELLS IN TRYPANOSOMA-MUSCULI INFECTION - DELAY OF IMMUNOLOGICAL CURE IN YOUNG MICE AND THE WEAK ABILITY OF AGED MICE TO CONTROL THE INFECTION( T)

After a 3 week course (approximately), during which there is marked ly mphoid hyperplasia, Trypanosoma musculi infections in young-adult mice are cured by an immune mechanism involving antibodies of the IgG2a is otype. Both the lymphoid hyperplasia and lgG2a antibody response are T -cell-dependent events and both processes appear to be defective in ag ed mice. The purpose of the studies reported here was to elucidate the effects of T. musculi infection on subsets of T cells for two reasons : (i) to gain insight into the probable roles of selected cytokines (I L-2, IL-4 and IFN-gamma) in facilitating the production of curative, I gG2a antibodies, and (ii) to examine the hypothesis that aging affects the competence of CD4(+) T cells to participate in immunological cont rol of infections. The major conclusions from these studies are that: (i) T. musculi infection of mice induces rapid change in the CD4(+) T cell population toward predominance of the activated or memory (CD45RB (lo)CD44(hi)) phenotype, cells which produce IFN-gamma II-3, IL-4 and IL-5, accompanied by profound inhibition of IL-2 production, and (ii) in the old mice these changes are superimposed on the natural age-asso ciated changes in the same direction (i.e. toward predominance of CD45 RB(lo)CD44(hi) T cells). Thus, in the old animals, the combined change s of aging and infection, moving in the same direction, are devastatin g, resulting in the aged animals being unable, or barely able, to cont rol infection.