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The Effect of Immunoregulatory Globulin (IRA) upon Lymphocytes in Vitro¹

From the Departments of Medicine, Microbiology, Surgery and Biochemistry, Boston University School of Medicine, Boston, Massachusetts 02118

Abstract

An immunosuppressive factor has been extracted from globulin containing fractions of human plasma proteins, which we have called "immunoregulatory globubin" (IRA). Cohn fraction IV has been found to contain this material. The IRA has been assayed by its ability to inhibit human blood lymphocyte proliferation induced in vitro by phytohemagglutinin (PHA). The IRA has been effective in reducing PHA-induced proliferation by 75% at doses as low as 0.2 mg/10⁶ cells in 1 ml of culture. Most fractions, however, were active at 2 to 3 mg/ml. We have also found the IRA to suppress lymphocyte proliferation induced by anti-human thymocyte serum and specific antigens. The concentration of IRA necessary to inhibit these weaker mitogenic stimuli was considerably less than that necessary to inhibit PHA response.

The IRA does not act by cytotoxicity, contains no cortisol and does not appear to interact sterically with the stimulating agents. The IRA is not firmly bound to lymphocytes. In inhibiting the PHA response, IRA behaves as a noncompetitive antagonist of the early metabolic events which lead to "lymphocyte activation."

Footnotes

¹ This work was supported in part by United States Public Health Service Grants AI 08579, FR 05390, AM 10824, GM 10374, and GM 32160; Massachusetts Heart Association Grant 896; Medical Foundation Grant, Massachusetts Division of the American Cancer Society Grant-In-Aid; and Army Contract DA 49193 MD 2621.

² Recipient of United States Public Health Service Career Development Award AI 39,096.

³ National Institutes of Health Trainee in Academic Surgery.