Amphibia occupy a crucial evolutionary position and therefore provide us with the opportunity to gain understanding of how the extraordinary complexity of mammalian immunity may have developed. I have been studying three species which offer a clear evolutionary and functional immunologic progression. My interest has centered primarily on the several regulatory roles of thymus-derived cells and macrophages. I plan to continue to explore T-cell regulation of antibody production in vitro by using specific lectins and antibodies for sorting and behavioral modulation. Our studies on immunologic regulatory changes during amphibian metamorphosis suggest that these models are especially well suited for tests of systemic (neuro-endocrine) control of different aspects of immune responses, e.g. antigen recognition, antibody production and particularly, thymic regulation. Additionally, amphibia, unlike mammals, affect much less subtle thymic regulation of responses to linear polysaccharides, e.g. Ficoll. Moreover, since amphibia can be more easily tolerized to these responses than others, they are useful for studying questions on self-tolerance. Since primitive vertebrates fail to respond to soluble protein antigens because of limited macrophage capacity, I plan to compare the capacities of primitive and more advanced amphibian macrophages to process and present antigen by using radiolabelled ovalbumin. My long term objectives are to understand the bases for mammalian immunologic failures by learning how their too finely tuned and fragile immune systems arose.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
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Immunobiology Study Section (IMB)
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Reed College
Schools of Arts and Sciences
United States
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Ruben, L N; Langeberg, L; Malley, A et al. (1990) A monoclonal mouse anti-human IL-2 receptor antibody (anti-Tac) will recognize molecules on the surface of Xenopus laevis immunocytes which specifically bind rIL-2 and are only slightly larger than the human Tac protein. Immunol Lett 24:117-25
Ruben, L N; Clothier, R H; Murphy, G L et al. (1989) Thyroid function and immune reactivity during metamorphosis in Xenopus laevis, the South African clawed toad. Gen Comp Endocrinol 76:128-38
Ruben, L N; Clothier, R H; Horton, J D et al. (1989) Amphibian metamorphosis: an immunologic opportunity! Bioessays 10:8-12
Horton, J D; Horton, T L; Varley, C A et al. (1989) Attempts to break perimetamorphically induced skin graft tolerance by treatment of Xenopus with cyclophosphamide and interleukin-2. Transplantation 47:883-7
Clothier, R H; Kandola, L; Mirchandani, M et al. (1988) Responses in Xenopus to the thymus independent antigen polyvinylpyrrolidone (PVP) and its haptenated derivative, trinitrophenylated PVP (TNP-PVP). Cell Differ 23:213-20
Ruben, L N; Beadling, C; Langeberg, L et al. (1988) The substitution of carrier priming of helper function in the common American newt, Notophthalmus viridescens by lectins and human lymphokines. Thymus 11:77-87
Marx, M; Ruben, L N; Nobis, C et al. (1987) Compromised T-cell regulatory functions during anuran metamorphosis: the role of corticosteroids. Prog Clin Biol Res 233:129-40
Highet, A B; Ruben, L N (1987) Corticosteroid regulation of IL-1 production may be responsible for deficient immune suppressor function during the metamorphosis of Xenopus laevis, the South African clawed toad. Immunopharmacology 13:149-55
Langeberg, L; Ruben, L N; Clothier, R H et al. (1987) The characterization of the toad splenocytes which bind mouse anti-human IL-2 receptor antibody. Immunol Lett 16:43-8
Ruben, L N; Clothier, R H; Mirchandani, M et al. (1987) Signals provided in vivo by human rIL-2 and Con A can switch hapten-specific tolerance from unresponsiveness to responsiveness in the South African clawed toad. Immunology 61:235-41

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