During the next five years it is planned to carry out in depth studies on the cellular and molecular mechanisms involved in the dramatic enhancement of immune responses in aged mice by IL-2 and 8-mercaptoguanosine (8MGuo). Although both of these substances overcome certain critical defects in the immune response, they differ in that IL-2 acts early in the immune response while 8MGuo reacts late. Furthermore, although they both have reactivity for T and B cells, IL-2 preferentially acts on T cells while the effect of 8MGuo is primarily on B cells. The interaction between IL-2 and 8MGuo and their interaction with other lymphokines in reconstituting age-associated immunity will be examined as well as their effects on the generation of other lymphokines and IL-2 receptors (IL-2R). Along the latter lines, the effect of aging on both the density of IL-2R, the frequency of IL-2R cells and their responsiveness to IL-2 will be established. Whether there is an association of the loss of both T and B cell precursor frequencies with age and whether the reconstitution of their expression can be induced by IL-2 or 8MGuo will be determined to establish if this loss is a mechanism involved in aging. Although 8MGuo is primarily a B cell activator, its synergy with T cells and T cell products suggests its effect on correction of defects in the immune response of aged mice may be in part through the T helper cell. The presence and function of T suppressor cells will be determined and compared in lymphocytes of young adults and aged mice. If suppression activity is enhanced in aged mice, the ability of 8MGuo or IL-2 to overcome such suppression will be determined. The above studies will be carried out with lymphocytes obtained from both Peyer's patch (PP) and spleen cells since the immune response of the latter tissue is extremely sensitive to age while that of the former is resistant. Thus, a comparison of the association of immunodeficiencies with cellular or molecular changes during aging between these two tissues will reveal which changes accompanying aging are responsible for the loss in immune reactivity.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
2R01AG000783-09A1
Application #
3114111
Study Section
Immunobiology Study Section (IMB)
Project Start
1978-01-01
Project End
1990-05-31
Budget Start
1987-06-01
Budget End
1988-05-31
Support Year
9
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Scripps Research Institute
Department
Type
DUNS #
City
San Diego
State
CA
Country
United States
Zip Code
92037