![]() ![]() For Candida immunizations, heat-inactivated C. On d 21, selected mice were footpad tested with 1e6 CFU of MRSA that was culture-verified killed after heating to 65☌ for 45 min. On d 7 and 14, mice were infected with 1e8 CFU suspended in IFA. To immunize with MRSA (USA300LAC strain from Frank DeLeo, NIAID), mice were infected subcutaneously with 1e8 CFU suspended in CFA on d 0. On d 21, a select number of mice were injected with 50 μg OVA or BSA into 1 hind paw, and 18–24 h later, the resultant difference in thickness between the injected paw and noninjected paw was measured to assure adequate sensitization (calipers L. The emulsion (40 μl) was injected subcutaneously, just superior to the tail. Emulsions were generated in Micro-Mate glass syringes (Popper and Sons, Hyde Park, NY, USA). Louis, MO, USA) and CFA (BD Difco Thermo Fisher Scientific, Waltham, MA, USA) was made so that both products had final concentrations of 2.5 μg/μl. All experiments were done in compliance with the guidelines of the NIAID Institutional Animal Care and Use Committee.Īn emulsion of OVA or BSA (Sigma, St. Mice from which antigen-naïve splenocytes were harvested and mice treated with DLE were also BALB/cJ, unless specified in figure legends. Experiments in BALB/c were repeated in mice purchased from Taconic Farms (Hudson, NY, USA). Experiments were performed in both male and female mice, but age and sex matched within each experiment. Mice were used between 7 and 12 wk of age. IL-17A/F dko mice were a kind gift from Rachael Caspi (NEI, Bethesda, MD, USA). OFFICE DEPOT SAN DISK MICROMATE SKINStat3 transgenic mice were a kind gift from John O’Shea (National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, MD, USA). TLR4 −/− mice, also deficient in the LPS-inactivating enzyme acyloxyacyl hydrolase, were a kind gift from Robert Munford (NIAID, Bethesda, MD, USA). We show that this passive cellular immunity is functional in both mice and humans and provides insights into the mechanistic basis and therapeutic potential of DLE.īALB/cJ, C57BL/6J, OT-I, OT-II, IFN-γ −/−, and C3H mice were purchased from The Jackson Laboratory (Bar Harbor, ME, USA). We show that the reportedly small, <8 kDa size of DLE activity is likely a reflection of past techniques and that instead, larger proteins are present, including bioactive TCR β chain and S100a9. ![]() We have further identified that DLE activity resides in antigen-specific CD8 + T cells and acts on antigen-loaded APCs to induce IL-6, which subsequently stimulates bystander memory CD8 + T cells. In approaching these historical reports with an open mind and modern techniques, we have confirmed transfer of immunity by DLE. However, earnest investigation into passive cellular immunity has largely ceased in recent decades, likely a consequence of both experimental inconsistencies and waning therapeutic interest subsequent to the discoveries of HIV and hepatitis C. The term DLE replaced transfer factor to better reflect the uncertainty of the lysate’s potential mechanisms. Reports following the discovery of the maternal transfer of antibodies asserted that dialyzed bovine colostrum activated similar pathways as leukocyte extracts but failed to clarify if these findings were attributable to the same mechanisms. Subsequent to its initial description, numerous claims surrounding transfer factor emerged, including enhanced wound healing, improved leukocyte chemotaxis, and anti-neoplastic activity. OFFICE DEPOT SAN DISK MICROMATE TRIALUncontrolled case series reported a benefit in diseases, including tuberculosis and CMC, and a double-blind, placebo-controlled clinical trial showed protection against leukemia-related varicella zoster virus. This dialyzed cellular lysate was entitled transfer factor for its ability seemingly to transfer immunity. ![]() This effect was reportedly within the dialyzable, <8 kDa fraction and was conserved between humans and other mammals. Conversely, lysates from donors who were diphtheria toxin DTH + but PPD − only enhanced recipient diphtheria toxin immunity but not tuberculin reactivity. The leukocyte lysate from human donors with a positive DTH test to tuberculin (PPD +) but a negative DTH test to diphtheria appeared to transfer tuberculin reactivity passively to subjects who were previously PPD − without impacting reactivity to diphtheria toxin. However, lysis of these cells reportedly did not fully negate their immunity-transferring properties. The ability of cells from immunized guinea pigs to transfer immunity against infectious agents to naïve guinea pigs established the presence of cellular immunity. ![]()
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