INTRODUCTION
Transfer factor (TF), also known as LawrenceTF, is an immunologic concept developed by Sherwood Lawrence, a highly-decorated immunologist, the former chair of New York University’s Division of Infectious Disease and Cancer Institute, a member of the National Academy of Sciences, and the founder and editor of Cellular Immunology. The immunologic concept supported by extensive experimental data developed by Lawrence in 1949 was that antigen-specific cell-mediated immunity (CMI) found in dialyzable leukocyte extract (DLE) from an individual sensitive to an antigen could then be transferred to an individual not sensitive to the same antigen.2 His experiments showed that transferring lymphocytes from a PPD-positive donor to a tuberculin-naïve recipient resulted in the conversion of the recipient to skin-test positivity.3 At a time when the leading thought was that all immunological phenomena were mediated through antibodies, the idea that lymphocytes produced other immunological molecules that could transfer specific immune memory from patient to patient had radical implications for treating a variety of illnesses. Lawrence’s original idea of transferring CMI involved the subcutaneous or intramuscular injection of dialyzable lymphocyte products smaller than 20 kilodaltons, as immunoglobulins were known to be 150 kilodaltons or larger. Of course, there is little specificity in injection of all particles smaller than 150 kilodaltons. Antigen-specific TF was later discovered to be 3500 Daltons, and this was what was later known as DLE. Unfortunately, most TF research halted in the 1980s with the first blood screening tests for HIV and the fear of contracting HIV through blood-borne products. In addition, a scandal from two researchers at Harvard working with TF who note that “original positive results may not have been obtained by the procedures described” further tarnished TF’s image in the scientific community.4 Although the culmination of such events set back research on TF for decades, recent research by Myles et al regarding antigen-specific DLE from CD8+ T cells has both renewed interest in TF research and suggested that TF may be able to be mass produced from a CD8+ cell line instead of extracted from donors.1
Characterization of TF
In the 1950s, the idea that such small molecules could convey specific immunological properties, such as delayed type hypersensitivity (DTH), was a novel proposition.5 It was a new concept that cells could effectively communicate with each other across relatively large distances through soluble messengers that were not immunoglobulins.6 But as the decades went on, there were more published reports of these biologically active substances, with some even capable of augmenting CMI.7 Since the 1980s, we have discovered a multitude of molecules able to convey information and impact resulting immune responses, and any individual or mixture of these chemicals can be responsible for the effects for TF. Most recently, non-coding
