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PubMed1974

In vitro properties of leukocyte dialysates containing transfer factor.

The chief impediment to the precise biochemical identification of transfer factor and its mechanism of action has been the lack of a reproducible in vitro assay. We now report on a method by which dialysates containing transfer factor of proven in vivo potency can convert nonimmune lymphocytes to immune responsiveness in vitro, as reflected by antigen-triggered lymphocyte proliferation. However, "water-dialyzed transfer factor" (TF(D)) prepared for in vivo use by the conventional method of dialysis against large volumes of water exhibits diminished activity in vitro and is frequently toxic to lymphocyte cultures. This problem can be avoided by dialysis of transfer factor into tissue culture medium. When this precaution is taken, such "media-dialyzed transfer factor" (TF(DM)) causes nonimmune lymphocytes to respond to antigen by an increment of thymidine incorporation that ranges from 2 to 25 times that of such cells cultured with antigen alone. This response is generally observed only in the presence of those antigens to which the TF(DM) donor expresses delayed cutaneous reactivity and is distinguishable from nonspecific adjuvant effects.

Adjuvants, Immunologic↗
PubMed2000

Soil-to-plant transfer factors for radiocesium and radiostrontium in agricultural systems.

A database of soil-to-plant transfer factors for radiocesium and radiostrontium has been compiled for arable crops from published and unpublished sources. The database is more extensive than previous compilations of data published by the International Union of Radioecologists, containing new information for Scandinavia and Greece in particular. It also contains ancillary data on important soil characteristics. The database is sub-divided into 28 soil-crop combinations, covering four soil types and seven crop groups. Statistical analyses showed that transfer factors for radiocesium could not generally be predicted as a function of climatic region, type of experiment, age of contamination, or soil characteristics. However, significant relationships accounting for more than 30% of the variability in transfer factor were identified between transfer factors for radiostrontium and soil pH/organic matter status for a few soil-crop combinations. Best estimate transfer factors for radiocesium and radiostrontium were calculated for 28 soil-crop combinations, based on their geometric means: only the edible parts were considered. To predict the likely value of future individual transfer factors, 95% confidence intervals were also derived. A comparison of best estimate transfer factors derived in this study with recommended values published by the International Union of Radioecologists in 1989 and 1992 was made for comparable soil-crop groupings. Whilst there were no significant differences between the best estimate values derived in this study and the 1992 data, radiological assessments that still use 1989 data may be unnecessarily cautious.

Agriculture↗
PubMed1987

Augmentation of skin test reactivity and lymphocyte blastogenesis in patients with AIDS treated with transfer factor.

Nine patients with the acquired immunodeficiency syndrome (AIDS) were administered four doses of pooled transfer factor obtained from the lymphocytes of three healthy controls and three homosexuals with stable lymphadenopathy and serum antibody to the human immunodeficiency virus. Before receiving transfer factor, all patients exhibited anergy to skin test antigens. After four weeks of transfer factor therapy, six of seven patients tested had at least one skin test response. Lymphocyte blastogenic responses to phytohemagglutinin rose from a stimulation index of 6.77 +/- 1.31 before treatment to 19.77 +/- 6.24 after four weeks of transfer factor therapy. Smaller but significant increases were also seen in blastogenic responses to antigens. Improvements in immune responses diminished after administration of transfer factor was halted. Thus, administration of transfer factor to patients with AIDS resulted in partial immune reconstitution. Further studies are indicated to examine the clinical efficacy of this immune response modifier in the treatment of AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1976

Transfer-factor therapy in multiple sclerosis.

The effect of transfer factor prepared from relatives of patients with multiple sclerosis (M.S.) and from unrelated donors on the clinical course of M.S. has been studied in fifteen male and fifteen female patients. Some patients were given transfer factor and some placebo (physiological saline). Results of three independent clinical examinations by different neurologists and subjective assessments by the patients showed no difference between those given transfer factor and those given placebo.

Adolescent↗
PubMed1976

Therapy with parent's lymphocyte transfer factor in children with infection and malnutrition.

Transfer factor (T.F.) prepared from 5 x 10(8) lymphoid cells from 500 ml of a parent's blood was given to 40 Australian aboriginal children aged 2-46 months who had been in hospital with acute infection. Many had protein-calorie malnutrition. These and a control group of 35 similar children were assessed blind for at least 12 months. In T.F.-treated children there were significantly fewer episodes of diarrhoeal disease for periods in excess of 26 weeks. Recurrent moderate diarrhoeal disease was particularly reduced, and the onset of severe gastroenteritis may have been delayed. There was no protection against chest, middle-ear, or skin infection.

Adult↗
PubMedDate not supplied

Effect of long-term therapy with transfer factor in rheumatoid arthritis.

Specific immunotherapy with transfer factor (TF) was used in a chronic experiment in a group of 50 female patients with rheumatoid arthritis (RA) stage I-III. The patients were followed up for 24 months, clinical and biologic examinations being repeated every 3 months. In this period the patients received beside the basic nonsteroid antiinflammatory therapy, one unit TF every week over a period of 6 months then one until TF every month (10 patients) to the end of experiment. Of the 50 patients 15 (30%) did not respond to the therapy and the experiments had to be interrupted after 6 months. Excellent, very good and good results were obtained in 35 patients (70%). In 12 patients the response was good but the dose of TF had to be increased to two units/week in the first 6 months. In 13 patients the results obtained were very good and therapy with nonsteroid products + TF was continued even after the first 6 months. In 10 patients with RA stage I the results obtained were excellent and after 6 months the nonsteroid therapy could be interrupted and the therapy was continued only with one unit TF every month. The study confirmed the fact that specific immunotherapy with TF represents an important adjuvant in the treatment of rheumatoid arthritis (RA).

Arthritis, Rheumatoid↗
PubMed2002

Isolation and characterization of cLV25, a Bacteroides fragilis chromosomal transfer factor resembling multiple Bacteroides sp. mobilizable transposons.

Horizontal DNA transfer contributes significantly to the dissemination of antibiotic resistance genes in Bacteroides fragilis. To further our understanding of DNA transfer in B. fragilis, we isolated and characterized a new transfer factor, cLV25. cLV25 was isolated from B. fragilis LV25 by its capture on the nonmobilizable Escherichia coli-Bacteroides shuttle vector pGAT400DeltaBglII. Similar to other Bacteroides sp. transfer factors, cLV25 was mobilized in E. coli by the conjugative plasmid R751. Using Tn1000 mutagenesis and deletion analysis of cLV25, two mobilization genes, bmgA and bmgB, were identified, whose predicted proteins have similarity to DNA relaxases and mobilization proteins, respectively. In particular, BmgA and BmgB were homologous to MocA and MocB, respectively, the two mobilization proteins of the B. fragilis mobilizable transposon Tn4399. A cis-acting origin of transfer (oriT) was localized to a 353-bp region that included nearly all of the intergenic region between bmgB and orf22 and overlapped with the 3' end of orf22. This oriT contained a putative nic site sequence but showed no significant similarity to the oriT regions of other transfer factors, including Tn4399. Despite the lack of sequence similarity between the oriTs of cLV25 and Tn4399, a mutation in the cLV25 putative DNA relaxase, bmgA, was partially complemented by Tn4399. In addition to the functional cross-reaction with Tn4399, a second distinguishing feature of cLV25 is that predicted proteins have similarity to proteins encoded not only by Tn4399 but by several Bacteroides sp. transfer factors, including NBU1, NBU2, CTnDOT, Tn4555, and Tn5520.

Bacteroides fragilis↗
PubMed1980

Chemoimmunotherapy of disseminated malignant melanoma with DTIC-BCG, transfer factor + melphalan.

The experimental synergism of melphalan with DTIC and the ability of transfer factor to improve immunocompetence were the basis of an attempt to improve therapeutic results in disseminated malignant melanoma. Sixty-four evaluable patients with disseminated malignant melanoma were treated in a 21-day cycle as follows: DTIC 250 mg/M2 intravenously days 1 to 5, Connaught BCG 6 X 10(8) organisms on days 7, 12, and 17 by scarification, and transfer factor 1 unit (10(9) lymphocytes equivalent, from immunocompetent relatives of patients) subcutaneously on day 12, with or without L-PAM 30 mg/M2 on day 1. Twenty-nine patients received L-PAM and 35 did not. Remission rates of 17% and 23%, respectively, occurred in these groups. An additional 15 patients received DTIC-BCG and three doses of transfer factor on days 7, 12, and 17 and had a remission rate of 20%. Remission duration and survival were compared to historical controls of 111 patients treated with DTIC and 89 treated with DTIC-BCG. Median survival on DTIC-BCG-Transfer Factor was seven months compared to four months for DTIC (P = .003) but did not differ from DTIC-BCG. Addition of L-PAM did not improve remission duration or survival compared to DTIC-BCG but enhanced myelosuppression and immunosuppression. A 60% increase in delayed type hypersensitivity to recall antigens occurred in this study compared to 34% with DTIC-BCG (P = .005). Prognosis and immunocompetence were not directly related. In summary, in this study, (1) transfer factor therapy did not enhance the clinical effects of DTIC-BCG, although it augmented delayed type hypersensitivity to recall antigens; and (2) L-PAM was not additive to DTIC in the treatment of disseminated malignant melanoma and may have abrogated the effect of immunotherapy.

Adult↗
PubMed1979

A placebo controlled clinical trial of transfer factor in lepromatous leprosy.

The effects of repeated injections of transfer factor over a period of 20 weeks were investigated in fourteen bacteriologically positive patients at the lepromatous side of the leprosy spectrum. All patients showed negative (0 mm induration) skin tests to M. leprae antigens (i.e. leprolin and lepromin). Of these patients, seven were treated with transfer factor with a total of 9 units (1 unit being equivalent to 5 x 10(8) lymphocytes) and seven with a placebo. Maintenance treatment with clofazimine was continued. Transfer factor was prepared from the lymphocytes of donors who showed positive skin tests to M. leprae antigens (i.e. leprolin greater than or equal to 12 mm induration, average 15.5 mm or lepromin greater than or equal to 8 mm induration, average 13.6 mm), as well as a positive lymphocyte transformation in vitro to M. leprae (the average transformation being higher than the average transformation of lymphocytes of tuberculoid leprosy patients). No differences were found between the two groups as regards the clinical course of the disease, the histopathological and bacteriological evaluation of skin biopsies, changes in skin test reactivity to various antigens (i.e. lepromin, leprolin, PPD, Mumps, C. albicans, Tr. rubrum and Varidase), as well as the lymphocyte transformation in vitro to various mitogens (i.e. PHA, PWM, Con A) and antigens (i.e. M. leprae, leprolin, PPD, BCG, Mumps, C. albicans, Trichophyton and Varidase). No evidence was found to suggest that transfer factor is a valuable adjuvant in the treatment of lepromatous leprosy patients or that it increases cell-mediated immune reactivity towards M. leprae.

Antigens, Bacterial↗
PubMed1975

Stimulation of monocyte cGMP by leukocyte dialysates. An antigen-independent property of dialyzable transfer factor.

We studied the effects of dialysates from leukocyte lysates containing dialyzable transfer factor activity and other leukocyte dialysates devoid of transfer factor activity on accumulation of cyclic nucleotides in human leukocytes. Dialysates from normal leukocytes produced 4- to 11-fold increases in leukocyte cGMP, and experiments with purified cell populations revealed that the increases were predominantly, if not entirely, in blood monocytes. Substances that increased monocyte cGMP could be obtained from several cell populations including mononuclear cells from Hypaque-Ficoll gradients, plastic-adherent monocytes, nonadherent lymphocytes, and neutrophils, but were not present in dialysates of leukemic lymphocytes from patients with the Sezary syndrome. Moreover, dialysates that increased leukocyte cGMP had essentially no effect on intracellular cAMP. Dialysates of lysed mononuclear cells contained serotonin, ascorbate, and an unidentified cholinergic activity, agents known to increase leukocyte cGMP. After passage of dialyzable transfer factor from mononuclear cells through a gel-filtration column, four fractions were obtained that increased leukocyte cGMP. Two of these fractions contained ascorbate; two other active fractions, including one that also caused conversion of delayed skin tests, did not contain detectable ascorbate or serotonin. The dialysate of lysed neutrophils also increased cGMP, but this activity was limited to the column fractions which contained ascorbic acid. These observations raise the possibility that alterations in monocyte cGMP content could modulate either the specific antigen-dependent, or, more likely, the antigen-independent activities in preparations of transfer factor.

Ascorbic Acid↗
PubMed1977

Disseminated varicella infection: treatment with transfer factor in a patient with Hodgkin's disease.

Treatment with transfer factor in a patient with disseminated varicella infection complicating stage IV Hodgkin's disease is described. The patient, a 24-year-old woman, showed transient clinical improvement and restoration of immune response to varicella-zoster antigen after receiving transfer factor. Though she later died from septicaemia, further trials of treatment of disseminated viral infection in patients with Hodgkin's disease with transfer factor are indicated.

Adult↗
PubMed1980

Human T lymphcytes are enriched for transfer factor.

Using a canine local skin assay, we tested transfer factor prepared from three subpopulations of human peripheral blood mononuclear cells. T lymphocytes are enriched for transfer factor whereas adherent cells and nonadherent/nonrosetting cells are not. Thus, it appears as if transfer factor is a T cell lymphokine, the immunobiology of which is still unclear.

Animals↗