Immunological activities of transfer factors

Specificity

A major concern in transfer factor research is how molecules with molecular weights of 4.9-5.4 kDa can transfer antigen-specific immune responses. The mechanism of this specificity has not been defined, but the evidence for specificity is so strong that it must be considered in formulation of models for transfer factor activity. For example, Maurer prepared lysates of leukocytes from human donors who had received ethylene oxide-treated human serum.

These lysates would transfer delayed-type hypersensitivity to recipients that had not received the modified serum. Burger and associates examined transfer factor activity in blood leukocytes of donors both before and after they were sensitized with keyhole limpet hemocyanin (KLH). The preimmunization specimens did not contain KLH transfer factor activity, while the postimmunization materials transferred delayed hypersensitivity to 25 of 26 recipients. Petersen and associates and Kirkpatrick and coworkers used a murine model to examine specificity of transfer factors, including preparations from donors that were immunized with synthetic antigens composed of amino acid random copolymers. Their results are summarized in Table 1. Taken together, the findings of these reports make it essential to consider specificity in formulating hypotheses for the mechanisms of action of transfer factors.

Interactions between transfer factors and antigens

At one time it was proposed that transfer factors were composed of highly immunogenic forms of antigen. This model would explain the specificity of transfer factors. To test this hypothesis, Petersen and colleagues mixed transfer factors with the immunizing antigen and tested the ability of the mixtures to transfer delayed-type hypersensitivity to unimmun-ized recipients. Their results disclosed that mixing the transfer factor with the homologous antigen 'neutralized' the immunologic effects of the transfer factor. On the other hand, mixing the same transfer factor with a different antigen did not alter the activity of the transfer factor.

This observation provided evidence against antigenic units in the transfer factors. Of greater significance, it provided the basis for the affinity purification of individual transfer factors.

Transfer factors and delayed-type hypersensitivity

There are no in vitro assays for transfer factors. Therefore, the activity must be measured by in vivo assays such as transfer of delayed-type hypersensitivity to nonimmune recipients. In a murine system, the footpad swelling assay has been quantitated so that it can be used to follow changes in specific activity during purification.

Transfer factors and cytokine production

The immunologic consequences of administration of transfer factors have been described in clinical and experimental settings. The earliest reports concerned patients with the Wiskott-Aldrich syndrome, chronic coccidioidomycosis or chronic mucocutaneous candidiasis. Similar results were observed in each group of patients. The recipients acquired the ability to express the delayed-type hypersensitivity responses

Table 1 Specificity of transfer factors in assays of delayed hypersensitivity

Experiment Donor sensitivity Recipient

Antigen used Footpad response P

Table 1 Specificity of transfer factors in assays of delayed hypersensitivity

Experiment Donor sensitivity Recipient

Antigen used Footpad response P

(A mm x 10-*)

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