One important aspect of the human and animal immune system is the negative regulation of the immune responses that occur in response to the apparent presence of antigens. If no brake were placed on immune response, antibody-producing cells, for one example, would continue producing antibodies indefinitely. When the immune system is not appropriately regulated, several systemic malfunctions can occur. Defects of the operation of the immune system such as these have been associated with certain autoimmune disorders, in which the body reacts against its own tissue as if the tissue were a foreign body. Rheumatoid arthritis, multiple sclerosis, myasthenia gravis, lupus erthematosus, and insulin-dependent diabetes (type 1) are believed to be examples of such conditions.
The negative regulation of the immune system is believed to be controlled in part by cells known as "suppressor cells." Human suppressor cells include T8 cells (which are also known as T8.sup.+ or Leu.sup.+2 cells); there may be other human suppressor cells. Suppressor cells act in concert with other cells to bring about a normal immune response, what may be considered immune system homeostasis. Autoimmune defects of the type described above may result from insufficient production, potentiation, or operation (which are collectively referred to at times hereinafter as "activation") of suppressor cells.
Copending patent applications of the inventor describe methods for assaying amplifier immune reserve (Gottlieb, "Diagnostic Methods for Immune Function," Ser. No. 830,728) and suppressor reserve (Gottlieb, "Determination of Suppressor Functional Reserve," Ser. No. 832,016), functions of the human and animal immune system to which the present invention relates; the latter is particularly pertinent. An abstract published in March 1985 (Sizemore, Farmer, and Gottlieb, "Enhancement of nonspecific suppressor T cell activity by immunomodulators derived from human leukocyte dialysates," Fed. Proceedings 947, No. 3133) refers in general terms to various aspects of the procedures described herein.
Other useful background on amplifiers and suppressors is found in Gottlieb U.S. Pat. No. 4,468,379, in copending Gottlieb patent application Ser. No. 643,724, and in copending Gottlieb patent application Ser. No. 813,586. These and the preceding patent applications in various respects distinguish immunomodulators, of which amplifiers and suppressors are each subsets, from the "transfer factor" of prior art. Transfer factor, for example, has a specific effect with regard to a particular antigen, for which it is said to transfer immune response from donor to donee although the latter may never have been previously exposed to the antigen in question. Immunomodulators, however, are nonspecific and their administration generally affects immune response only with respect to antigens to which the donee has previously (or at least concurrently) been exposed.
It has been observed that rheumatoid arthritis patients may display decreased production of interleukin-2 (IL-2) and decreased natural killer (NK) cell activity. See Combe, Pope, Darnell, Kincaid, and Talal, 133 J. Immunol. 709 (1984); Combe, Pope, Fishbach, Dranell, Baron, and Talal, 59 Clin. Exp. Immunol. 520 (1985). These observations tend further to confirm the hypothesis that the disease has a significant immune system component, since production of IL-2 and NK cell activity are considered to reflect the state of the subject's immune system function.