THE USE OF REPORTER ANTIGENS IN THE POPLITEAL LYMPH-NODE ASSAY TO ASSESS IMMUNOMODULATION BY CHEMICALS

Various drugs and other chemicals can induce T-cell-dependent B-cell a ctivation which may lead to allergic or autoimmune-like diseases. Beca use the nature of the relevant (neo-) antigens is generally not known and probably depends on the chemical, we have explored the potential u se of reporter antigens to determine T-cell-dependent B-cell activatio n by chemicals. TNP-Ficoll and TNP-OVA were used for this purpose beca use they are recognized by the same TNP-specific B cells, but these ce lls require distinct costimulation for specific antibody production. I t was found that HgCl2, phenytoin, nitrofurantoin, and D-penicillamine stimulated IgG(1) production to both antigens, incomplete Freund's ad juvant, silica, and dimethylsulfoxide to TNP-OVA only, and LPS and hyd roxyl-amino procainamide to TNP-Ficoll alone. The diabetogene streptoz otocin did not enhance IgG(1) production, but may enhance a cellular r esponse instead. Tolerogens and a T-cell antigen without intrinsic adj uvant activity did not influence the responses. The IgG(1) production to TNP-Ficoll was local and transient, and did not always require T ce lls. In contrast, responses to TNP-OVA could be measured in serum, led to specific memory, and were strictly T-cell dependent. These results demonstrate that specific antibody production to reporter antigens in dicates immunostimulatory effects of chemicals more sensitive than PLN cell count and provides important mechanistic information. Moreover, with TNP-OVA as reporter antigen the kinetics and regulation of chemic ally enhanced immune responses can be studied without the need to know the relevant neo-antigens for each individual compound. (C) 1997 Acad emic Press.