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In this paper data are presented indicating that immunotherapy with monoclonal anti-idiotypic antibodies (MoAb anti-id) can provoke different responses in the B-cell tumour concerned. With respect to the course of disease during and after immunotherapy, the in vitro findings may very well explain the in vivo observations in the two patients (D.E.F., B.O.R.) with B-cell chronic lymphocytic leukaemia (B-CLL) who were treated with MoAb anti-id. After initial tumour reduction, there was a recurrence of tumour cells with altered functional and phenotypic properties. In both cases the recurring tumour cells still expressed the same idiotype. In one patient (D.F.F.) the phenotypic changes (a surface Ig change from IgM, IgG. igA. and IgD to weakly positive IgM and IgD) and functional changes (a 10-fold increase in [3H]thymidine uptake and a decreased idiotype secretion in vitro), together with the in vivo findings with respect to the course of disease-at relapse an impressive tumour regrowth rate with constant serum idiotype level-suggest that immunoselection might have taken place favouring the survival and relapse of a less mature, more aggressive tumour cell population with a lower idiotype expression. In the second patient (B.O.R.), the phenotypic changes (an isotype change from IgM and IgD to IgM with the loss of IgD, and a gradual decrease in expression of CD19 and CD24) and functional changes (a 10-fold increase of idiotype secretion in vitro), together with the in vivo finding that the serum idiotype level had increased 25-fold compared with the preimmunotherapy serum level with comparable tumour load, strongly suggest an immunotherapy-induced differentiation of the malignant B cell. We also describe an increased expression of CD74. detected by MoAb BoM22, on the recurring tumour cells of patient B.O R., whereas the expression of HLA-DP, -DQ and -DR did not change. The significance of this finding is unclear. [ABSTRACT FROM AUTHOR]

Anti-CD3 MoAbs arc widely used in T cell activation studies, and are effective in immunosuppressive therapy. We used a panel of mouse (m) anti-CD3 switch variant MoAbs of five different isotypes to study IL-6 release from accessory cells. Incubation of human (h) mononuclear cells with anti-CD3 MoAbs resulted in increased lL-6 levels with MoAbs of mIgGI and mIgG2a isotypes. with no effect of mIgG2b or mIgA. This suggested involvement of IgG Fc receptors (FcγR) in triggering IL-6 production. To evaluate the role of different FcγR molecules individually we used a panel of hFcγR-transfected mouse fibroblasts. and Jurkat T cells as a model. IL-6 secretion by CD32 transfectants expressing the hFcγRHa high-responder (HR) allelic form was triggered by mIgGl anti-CD3 MoAb, with no effect of four other isotypes. None of theanti-CD3 MoAbs induced IL-6 secretion by CD32 transfectants expressing either a variant of this receptor, containing only a single intracellular amino acid (CT-). the hFcγRIIa low-responder (LR) allelic form, or hFcγRIIb1. hFcγRI (CD64) transfectants exhibited IL-6 production after incubation with mIgG2a anti-CD3 MoAb, and to a lesser extent with mlgG2b. and mIgGI MoAb. Indirect involvement of T cells in triggering IL-6 secretion could be excluded by experiments in which transfectants were cultured with immobilized anti-CD3 MoAb. These data indicate that cross-linking of either hFcγRI, or hFcγRIIaHR by appropriate anti-CD3 MoAbs triggers IL-6 production of accessory cells, and not T cells. This may also take place in vivo during immunosuppressive therapy with anti-CD3 MoAbs. and related antibody-mediated immune responses. [ABSTRACT FROM AUTHOR]