AUGMENTATION OF ANTIGEN-SPECIFIC LYMPHOPROLIFERATIVE RESPONSES IN-VITRO BY BIOLOGICAL RESPONSE MODIFIERS

The detection of antigen-specific T cell responsiveness, particularly of resting memory lymphocytes, in cultures of peripheral blood mononuc lear cells (PBMC) may be hampered by a less than optimal antigen prese ntation in vitro. Augmented sensitivity of the test system may be achi eved by the addition of reagents with a beneficial effect on lymphocyt e and antigen-presenting cell (APC) functions. In this study the effec t of several biological response modifiers on antigen-specific T cell proliferation was determined, using nickel sulphate and tetanus toroid as test antigens. IL-1 alpha (100 U/ml), interferon-gamma (IFN-gamma) (10 U/ml), and indomethacin (2 mu M) were found to significantly enha nce nickel-induced proliferation in PBMC cultures from nickel-hypersen sitive donors (n = 6). Tetanus-induced proliferation (n = 5) was simil arly enhanced, both by the above supplements and by the addition of po lyethylene glycol (PEG) or a neuraminidase treatment of the PBMC befor e culture. The addition to PBMC cultures of a combination of IL-1 alph a (30 U/ml), IFN-gamma (10 U/ml), and indomethacin (2 mu M) is recomme nded to specifically enhance antigen-induced lymphoproliferative signa ls.