Immunologic Specificity of Transfer Factor

Zuckerman, Kenneth S.; Neidhart, James A.; Balcerzak, Stanley P.; LoBuglio, Albert F.

doi:10.1172/jci107841

Cited by 72 publications

(20 citation statements)

References 9 publications

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“…On the other hand, Fractions III-IV of mononuclear cell dialysates which did not contain ascorbic acid or serotonin, did promote an increase in cGMP content of the plastic-adherent mononuclear cells. Fraction IV was also found to contain the component(s) responsible for conversion of delayed skin responses, confirming the observations of Zuckerman and co-workers (20). While it is conceivable that the same component could both cause accumulation of cGMP and convey the information needed for the conversion of the immunologic response, it seems more likely to us that cGMP may be involved in regulation of the antigen-independent activities of transfer factor, especially 'Kirkpatrick, C. H. Unpublished observations.…”

Section: Introductionsupporting

confidence: 88%

“…Both pools were lyophilized and then reconstituted so that the extract from 3 X 10' cells was contained in each milliliter. Because of the previous report by Zuckerman et al (20), it was assumed that all of the transfer factor activity in the crude material would be contained in only one of the two pools. After Millipore filtration and sterility testing, 2 ml of a pool was injected subcutaneously into immunologically deficient patients for assessment of transfer factor activity.…”

Section: Introductionmentioning

confidence: 99%

“…Material from dialysates of either (6,7,13), T-lymphocyte-mediated cytotoxicity against allogeneic cells (9,10), and release of lysosomal enzymes from neutrophils (25,26 (30). The concept that transfer factor contains antigen-specific activities is supported by reports of transfer of delayed skin responses to nonenvironmental antigens such as denatured human serum albumin (31) and keyhole limpet hemocyanin (20), specific cytoxicity against tumor cells (4,5), and accelerated rejection of skin allografts (32). On the other hand, reports of appearance of immunologic responses in recipients of transfer factor or leukocyte lysates that were not present in the donor (3,(33)(34)(35)(36)(37) and the recent demonstration of chemotactic activity in transfer factor preparations (38) suggest that transfer factor contains adjuvant-like, antigen-independent activities.…”

Section: Introductionmentioning

confidence: 99%

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

Sandler¹,

Smith²,

Manganiello³

et al. 1975

J. Clin. Invest.

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A B S T R A C T 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 HypaqueFicoll 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

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Section: Introductionsupporting

confidence: 88%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

Sandler¹,

Smith²,

Manganiello³

et al. 1975

J. Clin. Invest.

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“…Fourteen days after footpad injection of ovalbumin (OA) or bovine gamma globulin (BGG) in complete Freund's adjuvant (8), a cell suspension in 4.0 ml of Hanks' balanced salt solution (Gibco) was prepared from the draining lymph nodes of a Hartley guinea pig. The cells were lysed by 10 freeze-thaw cycles, and centrifuged at 700 X g for 20 min at 220. The resulting supernatant was centrifuged at 20,000 X g for 40 min at 40, and the final supernatant was lyophilized, redissolved in 0.7 ml of water, and applied to a 1 X 66 cm Sephadex G-25 fine (Pharmacia) column.…”

Section: Methodsmentioning

confidence: 99%

Guinea pig transfer factor-like activity detected in vitro.

Dunnick¹,

Bach²

1975

Proc. Natl. Acad. Sci. U.S.A.

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"Transfer factor" was prepared by Sephadex G-25 chromatography of lymph node cell lysates from guinea pigs immunized with ovalbumin or bovine gamma globulin. Treatment of nonimmune peritoneal exudate cells with the transfer factor and specific antigen leads to inhibition of miration of the cells, whereas cells treated with the transfer factor alone or specific antigen alone are not inhibited from migrating. An average of 24-28% inhibition is observed in the presence of transfer factor and specific antigen, but only 5-15% inhibition in the presence of transfer factor and nonspecific antigen. The guinea pig transfer factor we have tested in vitro has some physical characteristics in common with human transfer factor.Transfer factor is defined as the dialyzable portion of human leukocyte extracts that transfers cellular immunity from immune to nonimmune individuals. This material is prepared from white blood cells of donors with positive skin tests and tested by injection into recipients with negative skin tests. At some later time, the recipients are skin tested; a successful transfer is indicated by erythema and induration 24 hr later at the site of antigen injection. Although several workers have reported successful transfers, neither the phenomenon nor the molecule are understood (1). A major problem has been the lack of easily reproduced transfers of cellular immunity by immune cell extracts in animal systems (2-5).We have studied a dialyzable activity of guinea pig immune cell lysates by an in vitro correlate of cellular immunity, the macrophage migration inhibition test. In this test, immune peritoneal exudate cells incubated with specific antigen are inhibited from migrating when compared to immune cells incubated with no antigen or a nonspecific antigen. Nonimmune peritoneal exudate cells migrate the same distance in the presence and absence of antigen. Thus, one might test the ability of transfer factor to convert nonimmune cells to the immune state by monitoring the migration inhibition "responses" to antigen of nonimmune cells treated with transfer factor. Since we test the "transfer factor" exclusively in vitro, the molecule or molecules we study may not be the same as those defined as transfer factor in human systems.Fireman et al. (6) and Asher et al. (7) have tested human transfer factor by the blastogenesis test, an in vitro correlate of cellular immunity. Their results indicate that preparations of human transfer factor, active in vivo, may also be active in vitro.MATERIALS AND METHODS Preparation of Transfer Factor. Fourteen days after footpad injection of ovalbumin (OA) or bovine gamma globulin (BGG) in complete Freund's adjuvant (8), a cell suspension in 4.0 ml of Hanks' balanced salt solution (Gibco) was prepared from the draining lymph nodes of a Hartley guinea pig. The cells were lysed by 10 freeze-thaw cycles, and centrifuged at 700 X g for 20 min at 220. The resulting supernatant was centrifuged at 20,000 X g for 40 min at 40, and the final supernatant was lyophilized, redissolved...

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“…Many investigators have shown that gel filtration of human TFd on Sephadex G-25 termed TFc or TFg produces a biologically active fraction with a character istic effluent volume and high 260 nm/280 nm ratio (Zuckerman et al 1974;O'Dorisio et al 1976;Tomar et al 1976). Such a fraction was considered to contain hypoxanthine as a major component (O'Dorisio et al 1976;Tomar et al 1976).…”

Section: Dose Response To Tfmentioning

confidence: 99%