Eosinophils (eos) are frequently associated with allergic and parasitic disease. Interactions between eos and other cellular components of the immune response may be critical to the expression of clinical disease. Our previous studies have established that eos (and eos extracts and supernatants) inhibit a T lymphocyte proliferative response at least in part by activation of Leu2b T suppressor cells. The proposed studies will focus on the role of eos extracts and supernatants in modulating T and B lymphocyte function. Specific questions to be investigated include (1) What is the mechanism of eosmediated suppression? What are the characteristics of eos- mediated activation of CD8+(Leu2b) T suppressor cells? Kinetics, dose response curves, and quantitative comparisons of inhibition of mitogenstimulated lymphocyte proliferation will be examined. Which subsets of CD8+ Ts cells are activated? We will use antibody-complement lysis and FACS sorting to prepare Leu8- Ts effector and Leu8+ Ts amplifier cells to determine which subset(s) is responsive. Is B cell function inhibited by eos-mediated activation of Ts cells? This will be examined by quantitative determination of IgG and IgE. (2) What is the biochemical nature of the suppressor factor(s)? Appropriate protein chemistry techniques will be used for analysis. (3) Do atopic eos and/or lymphocytes have altered suppressive activity? We will prepare atopic eos and lymphocytes and test their interactions with normal cells. (4) Do hypodense eos have altered suppressive activity? This will be tested by preparing selected subpopulations of eos and comparing their suppressive activity with normal eos. In sum, these studies should provide insight into the immunoregulatory functions of eos and, as such, may ultimately offer new therapeutic options in allergic and parasitic disease.
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