No abstract

It has recently been described that monoclonal antibody OKT 3, that reacts with the T3 determinant on all peripheral T lymphocytes in man, is also mitogenic for T cells. We have produced two monoclonal antibodies (WT 31 and WT 32) which apparently react with the T3 antigen. We have now tested the mitogenic effect of these antibodies and compared it with the mitogenicity of three other anti-T3 monoclonal antibodies, OKT 3, UCHT 1 (ref. 4) and anti-Leu 4 (ref. 5). Two distinct patterns were observed. WT 32 and OKT 3, both of the IgG2a subclass, were mitogenic for human T cells in all cases studied. By contrast, WT 31, UCHT 1 and anti-Leu 4, all of the IgG1 subclass, were devoid of mitogenic effect in 30% of the individuals tested (non-responders). The mitogenicity of all five anti-T3 antibodies was fully dependent on the presence of monocytes. Addition of purified monocytes from a responder to purified lymphocytes from a non-responder induced responsiveness to both IgG1 and IgG2a anti-T3 antibodies. These results suggest that the polymorphism in the mitogenic effect of these IgG1 antibodies is caused by polymorphism in monocyte function, possibly at the level of the Fc receptor that reacts with mouse IgG1.

The hydrolases aminopeptidase A and dipeptidyl peptidase IV, both present in the kidney on the brush borders o f the proximal tubule epithelial cells and podocytes, are involved in the induction o f experimental membranous glomerulo nephritis in the mouse. However, little is known about their (co) distribution in other tissues and their function in health and disease. A detailed insight into the localization o f these two enzymes is a prerequisite to elucidation o f their func tion. Therefore, we investigated the presence and co-dis tribution o f aminopeptidase A and dipeptidyl peptidase IV by immunohistology with two different rat monoclonal antibodies, the specificity o f which was determined by an im m unodepletion technique. In addition, the molecular weight o f the hydrolases was analyzed by SDS-PAGE after isolation by solid-phase immunoprécipitation from glomer uli, renal brush borders, and thymus. Both hydrolases showed different molecular weights in renal corpuscle, renal brush borders, and thymic cells, A widespread organ distribution o f the two hydrolases was observed, with co-localization in kidney, liver, small intestine, thymus, brain, spleen, and lymph nodes, either on the same cells or on different cells in the same organ. This distribution and partial co-localiza tion suggests that the two hydrolases, acting either alone or in concert, have a role in many diverse biological processes.

To investigate whether the administration of cimetidine can improve the reliability of creatinine as a marker of GFR, we compared the creatinine clearance (CCr) to the clearance of the true filtration markers 51Cr-EDTA (CEDTA) and inulin (CIn), after oral ingestion of cimetidine in 10 healthy men and 29 patients with varying degrees of renal dysfunction. After administration of cimetidine for three to six days, serum creatinine level rose in all participants, while CEDTA and CIn remained stable in a subgroup of 14 subjects in whom they were measured before as well as after the administration of cimetidine. The mean (+/- SD) ratios of CCr to CEDTA (N = 39) and of CCr to CIn (N = 19) after ingestion of cimetidine were 1.02 +/- 0.13 and 1.01 +/- 0.13, respectively, and did not differ significantly from unity. This high degree of accuracy of the cimetidine-aided CCr was present over the entire range of renal function in the study population. Our results also indicated an improved precision of the cimetidine-aided measurement of CCr, resulting in a variability that did not differ significantly from that of the measurement of CEDTA or CIn. We conclude that after oral administration of cimetidine, the creatinine clearance can be used as a reliable measure of GFR within a broad range of renal function.

Highly reproducible anti glomerular basement membrane (GBM) nephritis has been induced in the mouse after a single injection of rabbit or goat antibody against purified homologous GBM. The severity of albuminuria was closely related to the amount of antibody given. With doses of 4 mg or more, low serum albumin concentrations, sometimes accompanied by ascites and oedema, were observed after 1 week. Glomerular injury was characterized by an initial accumulation of polymorphonuclear granulocytes followed by thrombosis and necrosis, the extent of which defined the outcome of the glomerulonephritis. With high doses of antibody the exudative lesions entered a chronic phase, while at doses lower than 2 mg remission of the lesions occurred. Immunofluorescence studies showed prompt linear fixation of the injected antibodies to the glomerular capillary wall, accompanied by immediate binding of C3 in a fine granular pattern. Fibrin deposits appeared at 2 h in some glomeruli, increased thereafter, and were present after one day in more than 90% of the glomeruli in mice that had received 4 mg of antibody. This new reproducible model in the mouse is suited for the study of the relationship between activation of mediator systems, histological lesions, and proteinuria.