Abstracts 181

be postulated to include an analogous cellular immune response through several mechanisms which will be discussed in detail. We induced tolerance in guinea pigs to human hepatitis B immunoglobulin. The guinea pigs were then sensitized to hepatitis B vaccine. When the animals were challenged for a delayed type hypersensitivity (DTH) response to the hepatitis B vaccine, the tolerant animals mounted a significantly greater response than the nontolerant animals. As a con- trol, the animals were sensitized and challenged with purified protein derivative at the same times. Tolerance induction to hepatitis B immunoglobulin had no effect on the D T H response to this unrelated antigen. This technique of using exogenous antibody as a signal to amplify the cellular immune response in a specific fashion may have broad implications for the treatment of malignancies and infections where a cellular immune response is important. These data may also ultimately aid in a better understanding of the cellular immune response and in particular how it is coupled to the humoral immune system. This latter point has special relevance to the field of organ transplantation where the cellular immune response is a major obstacle to allograft survival.

MODULATION OF HUMAN T CELL CLONE FUNCTION. G. Pawe|ec, E.M. Schneider, M. Essrich, M. Blaurock, H.-J. Biihring, and P. Wernet; Immunology Laboratory, Medizinische Klinik, D-7400 Tiibingen, FRG.

Recloning of interleukin-2 (IL-2)-dependent primed lymphocyte typing (PLT) clones revealed that the majority of subclones (ca. 65%) failed to respond to alloantigen, whereas the minority retained specific alloreactivity. Limiting dilution analysis of the frequency of reactive cells within alloproliferative clones supported this conclusion. The lack of reactivity of the majority of subclones may be related to our previous finding that without subcloning, PLT clones lost their antigen- specific responsiveness after extended culture, and suggests generation of intra- clonal heterogeneity resulting in the rapid selection of nonreactive variants. Fur- thermore, such "ex-PLT" clones acquired permanent suppressive activity for lymphoproliferative responses as well as for Ig secretion and colony formation by bone-marrow cells, and concurrently acquired the ability to induce suppressive populations in allogeneic or autologous lymphocytes, a property shared with natural killer-like clones. Suppressor cell induction required cell-cell contact, since lysed cells, or culture supernatants of viable cells, failed to generate suppres- sion. The suppressor induction activity of both types of clone was inhibited only by the "broad" anti-class II monoclonal antibody (MoAb) T1139 recognizing HLA-DR, DP, and additional antigens provisionally designated "DP-like," but not by anti-DR, DQ, or class I MoAb. Suppressive clones continued to express antigen receptor-associated CD3 structures and WT31 determinants, retained normal karyotypes, and dependency on IL-2. However , quantitative FACS anal- ysis showed that the density of DQ, DR, and DP antigens.on ex-PLT clones was reduced, but with a proportionally lesser decrease of TU39-positive antigens. Southern blot analysis of T cell receptor/3 chain gene rearrangements have thus far not indicated any alterations in restriction fragment length polymorphism patterns in ex-PLT clones compared to PLT-active cells from the same clone. A similar, but temporary, modulation of clonal function may be achieved by treating PLT clones with MoAb to CD3 antigens. This caused rapid disappearance of CD3 structures from the cell surface, and loss of responsiveness to alloantigen which was regained after 5 days in culture. When cells were tested for nonspecific suppression, it was found that CD3 modulation was paralleled by an acquired suppressive activity, which disappeared as CD3 determinants and antigen reac- tivity were re-expressed. Whether these two suppressor phenomena, one per- manent, the other temporary, share further similarities awaits clarification.