Trypanosoma musculi infections of mice are typified by phases of: Rapid growth of the parasites in the blood and peritoneal space (PS); """"""""plateau""""""""; and, after about 2 wk, rapid immune elimination and cure. During the course of infection immune responses are markedly inhibited. Initiation of immune elimination of the parasites coincides with the release from inhibition. We know little about: (a) immune processes that effect parasite elimination; (b) mechanisms responsible for the prolonged inhibition of immunity; or (c) events underlying the termination of inhibition and recovery of immune responses. We do know that there is variation among inbred mice in susceptibility to T. musculi and, especially, that aged animals suffer much more severe infections than young-adults. The murine/T. musculi infections; and (b) the causes of age-related deterioration of those processes. Major candidates for the immune processes are antibody (Ab)-dependent cytotoxicity (ADCC) and Ab-promoted hepatic phagocytosis. The component of these processes likely to suffer most from parasite-induced inhibition and age-related debilitation is the elaboration of humoral antibodies. We will study young and aged mice, of a susceptible and resistant strain, with respect to: (a) the quantity and quality of parasite-specific antibodies generated during infections; (b) the types and competence of ADCC effector cells and (c) the efficiency of hepatic clearance. Clones of T. musculi and a panel of monoclonal antibodies (at hand) will aid the investigation. The restriction of interleukin 2 availability by the combined effects of aging and parasite infection will be explored. Suppressor cells will be studied. This research will reveal much about the nature of the deterioration of immune processes that expose the aged individual to infections.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG006278-02
Application #
3117236
Study Section
Tropical Medicine and Parasitology Study Section (TMP)
Project Start
1985-09-30
Project End
1989-08-31
Budget Start
1986-09-01
Budget End
1987-08-31
Support Year
2
Fiscal Year
1986
Total Cost
Indirect Cost
Name
George Washington University
Department
Type
Schools of Medicine
DUNS #
City
Washington
State
DC
Country
United States
Zip Code
20052
Albright, J W; Zuniga-Pflucker, J C; Albright, J F (1995) Transcriptional control of IL-2 and IL-4 in T cells of young and old mice. Cell Immunol 164:170-5
Albright, J W; Stewart, M J; Latham, P S et al. (1994) Antibody-facilitated macrophage killing of Trypanosoma musculi is an extracellular process as studied in several variations of an in vitro analytical system. J Leukoc Biol 56:636-43
Albright, J W; Albright, J F (1994) Ageing alters the competence of the immune system to control parasitic infection. Immunol Lett 40:279-85
Utsuyama, M; Albright, J W; Holmes, K L et al. (1994) Changes in the subsets of CD4+ T cells in Trypanosoma musculi infection: delay of immunological cure in young mice and the weak ability of aged mice to control the infection. Int Immunol 6:1107-15
Albright, J W; Holmes, K L; Albright, J F (1990) Fluctuations in subsets of splenocytes and isotypes of Ig in young adult and aged mice resulting from Trypanosoma musculi infections. J Immunol 144:3970-9
Albright, J W; Pierantoni, M; Albright, J F (1990) Immune and nonimmune regulation of the population of Trypanosoma musculi in infected host mice. Infect Immun 58:1757-62
Albright, J W; Long, G W; Albright, J F (1990) The liver as a major site of immunological elimination of murine trypanosome infection, demonstrated with the liver perfusion model. Infect Immun 58:1965-70
Albright, J W; Albright, J F (1989) Immunological and nonimmunological control of severity of Trypanosoma musculi infections in C3H and C57BL/6 inbred mice. Infect Immun 57:1647-55
Albright, J W; Matusewicz, N M; Albright, J F (1988) Aging of the murine immune system is reflected by declining ability to generate antibodies that promote elimination of Trypanosoma musculi. J Immunol 141:1318-25
Albright, J W; Albright, J F (1988) The availability of purines influences both the number of parasites and the splenocyte levels of purine-metabolizing enzymes in trypanosome-infected mice. Infect Immun 56:831-5

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