In this study, we have used a mouse monoclonal antibody to rat Ia (RT1-B or class II) antigens to demonstrate, by immunofluorescence on frozen sections, intensely Ia-positive dendritic cells in the interstitial connective tissues of every tissue we have examined (heart, liver, thyroid, pancreas, skin, kidney, ureter, and bladder) with the striking exception of brain. The characteristics of the interstitial dendritic cell found in heart were studied in detail, and this cell was shown to be negative for acid phosphatase, beta-glucuronidase, and ATPase activity, and certainly some and probably all of the cells were negative for nonspecific esterase activity. Experiments with colloidal carbon suggested that the cell was either poorly or not at all phagocytic. The cells were negative for surface immunoglobulin and the W3/13 antigen, but positive for the leukocyte common antigen and the SD (Class I) antigens of the major histocompatibility complex. The cell was shown to be of bone marrow origin, and either the cell itself, or more probably its precursor, was shown to be sensitive to irradiation and to cyclophosphamide. All strains tested--including the nude rat--had large numbers of interstitial dendritic cells. The widespread distribution, except in brain, of this cell, which resembles in every respect the dendritic cell described by Steinman et al. (4) in the spleen and lymph nodes of the mouse, is of interest, and the implications in this finding are discussed.

No abstract

Spleen cells from a BALB/c mouse that had been immunized with human thymocytes were fused with the myeloma line P3-NS 1/1 Ag 4.1. One of the resulting hybrid clones (NA 1/34) secreted an antibody that was highly specific for human thymocytes. Eighty-five % of thymocytes expressed the antigen designated HTA1. There were an estimated 15 x 10(4) molecules of HTA 1 per cell, and it is therefore a major surface molecule. The expression of this antigen on thymocytes appears to be reciprocal to HLA, as recognized by another monoclonal antibody W6/32. Immunoprecipitated material from [125I]-labeled thymocyte membranes was analyzed by polyacrylamide gel electrophoresis in sodium dodecyl sulfate which disclosed a single component of 45,000 molecular weight.

SummaryLEW (RT1 l) rats were immunized with peptides corresponding to the c~ helical region of the oll domain (peptide 1), the fl sheet of the oe2 domain (peptide 2), and the a helical region of the c~2 domain (peptide 3) of the RT1-A avl classical class I molecule of the DA (RT1 'vl) strain. The immunizations were without carriers, and the objective was to prime to indirect allorecognition without influencing direct recognition of the RT1-A avl molecule. The LEW rats mounted strong primary and secondary antibody responses to peptides 1 and 3, but only weak secondary responses to peptide 2. None of the antipeptide antibodies crossreacted with intact RT1-A a~l class I molecules. The immunizations also resulted in LEW antigen-presenting cell-dependent, CD4 + T cell proliferative responses, which were very strong against peptide 1 and weakest against peptide 2. LEW rats immunized with peptides 1 or 3, but most effectively with both peptides 1 and 3 together, showed accelerated rejection of DA skin allografts. This effect was not observed in LEW rats immunized with peptide 2. In response to the DA skin aUograft, the peptide-immunized LEW rats showed markedly accelerated kinetics of antibody production to the intact RT1-A ~1 molecule. These data demonstrate that indirect allorecognition can play an important role in allograft rejection and have important implications for understanding allograft rejection and its regulation.

This study defines the cooperative nature of the binding of this vector system to target cells and establishes the cell types most likely to be effectively targeted for DNA transfer.

The strong allogeneic response to donor MHC molecules in transplantation and the weak response to tumor antigens represent two important and divergent but potentially interactive immune responses. A patient's response to allogeneic MHC molecules might promote an effective T-cell response to self MHC-restricted tumor peptides and the possibilities for this are discussed here. These allogeneic responses might successfully be harnessed to promote the immune eradication of metastatic cancer.

Hydrodynamic gene delivery is an attractive option for non-viral liver gene therapy, but requires evaluation of efficacy, safety and clinically applicable techniques in large animal models. We have evaluated retrograde delivery of DNA to the whole liver via the isolated segment of inferior vena cava (IVC) draining the hepatic veins. Pigs (18-20 kg weight) were given the pGL3 plasmid via two programmable syringe pumps in parallel. Volumes corresponding to 2% of body weight (360-400 ml) were delivered at 100 ml s À1 via a Y connector. The IVC segment pressure, portal venous pressure, arterial pressure, electrocardiogram (ECG) and pulse were monitored. Concurrent studies were performed in rats for interspecies comparisons. The hydrodynamic procedure generated intrahepatic vascular pressures of 101-126 mm Hg, which is B4 times higher than in rodents, but levels of gene delivery were B200-fold lower. Suprahepatic IVC clamping caused a fall in arterial pressure, with the development of ECG signs of myocardial ischaemia, but these abnormalities resolved rapidly. The IVC segment approach is a clinically acceptable approach to liver gene therapy. However, it is less effective in pigs than in rodents, possibly because of larger liver size or a less compliant connective tissue framework.

Persistent gambling was studied as a function of the reinforcement of arousal and winning during normal poker machine playing sessions. Play rate, heart rate, winnings, subjective excitement and expectations of winning were recorded for five male and five female high-frequency players. Autoregressive regression analysis indicated that wins affect play rate for up to three minutes, while effects of the other variables were inconsistent. Markov chain analysis confirmed that wins smaller than 50 credits tend to elevate play rate, while larger wins cause a breakdown in the otherwise very regular rate of play. Results are discussed in relation to the development of impaired control of gambling behaviour.