"Transfer Factor": An Update 1

Abstract

After a short burst of activity following Lawrence's original description of the transfer factor phenomenon (I), interest in this area diminished drastically. Historically, TF was defined functionally as a biochemical entity in dialyzable leukocyte extracts (DLE) which could transfer antigen-specific reactivity as demonstrated by skin testing; it has been shown lately by more sensitive and quantitative in vitro assays measuring lymphokine release by T lymphocytes incubated with the appropriate antigen (2). However, only recently has it been definitively proven that TF acts in an antigen-specific manner (3). Other components present in DLE can have anti-gen-independent, nonspecific effects on cellular immunity (CMI) and on the inflammatory response; among these are prosta-glandins, nicotinamide, ascorbic acid, serotonin, histamine, T lymphocyte or differentiation maturation factors, thymosin-like factor, monocyte chemoattractants, and neu-trophil immobilizing factors. These components might well produce either generalized augmentation or even suppression (4) of immunologic activities upon clinical DLE evaluation in vitro and in vivo. In the early seventies interest in the TF phenomenon was rejuvenated when our group showed that DLE containing TF, in addition to transferring skin-test reactivity, conferred both the ability to produce lymphokines in response to specific antigens and resistance to infection in patients with genetically determined immune deficiency. Since then, several groups successfully employed DLE in immunotherapy and/or immunoprophylaxis in diseases associated with compromised cellular immunity. These diseases have included acquired or inherited "antigen-specific" or "broad spectrum" immunodeficiency diseases, neoplasia, and a variety of viral, fungal, and mycobacterial diseases. In these patients, each had failed to respond previously to any of the available antibiotics or chemotherapy and/or developed strong adverse reactions. Each patient treated with DLE served as his own control in that upon receiving DLE devoid of TF of the appropriate specificity, disease as measured by both clinical response or laboratory parameters worsened dramatically; however, DLE therapy containing TF of the correct specificity was substantially more clinically dramatic.