Pilot Study Evaluating Regulatory T Cell-Promoting Immunosuppression and Nonimmunogenic Donor Antigen Delivery in a Nonhuman Primate Islet Allotransplantation Model.

The full potential of islet transplantation will only be realized through the development of tolerogenic regimens that obviate the need for maintenance immunosuppression. Here, we report an immunotherapy regimen that combines 1-ethyl-3-(3'-dimethylaminopropyl)-carbodiimide (ECDI)-treated donor lymphoid cell infusion (ECDI-DLI) with thymoglobulin, anti-interleukin-6 receptor antibody and rapamycin to achieve prolonged allogeneic islet graft survival in a nonhuman primate (NHP) model. Prolonged graft survival is associated with Treg expansion, donor-specific T cell hyporesponsiveness and a transient absence of donor-specific alloantibody production during the period of graft survival. This regimen shows promise for clinical translation.

Anti-CD45RB/anti-TIM-1-induced tolerance requires regulatory B cells.

The role of B cells in transplant tolerance remains unclear. Although B-cell depletion often prolongs graft survival, sometimes it results in more rapid rejection, suggesting that B cells may have regulatory activity. We previously demonstrated that tolerance induction by anti-CD45RB antibody requires recipient B cells. Here, we show that anti-CD45RB in combination with anti-TIM-1 antibody has a synergistic effect, inducing tolerance in all recipients in a mouse islet allograft model. This effect depends on the presence of recipient B cells, requires B-cell IL-10 activity, and is antigen-specific. These data suggest the existence of a regulatory B-cell population that promotes tolerance via an IL-10-dependent pathway.

Phase locking of a multimode to a single-mode He-Ne laser.

Two independent He-Ne lasers operating at 0.6328 microm were phase locked to a very high degree of coherence using feedback control. One of these lasers was single mode and the other multimode. The results suggest that the present technique can be used to generate high-power, coherent light pulses from an array of He-Ne lasers.

Cancer incidence in the Mexican-American.

Lower incidence rates of cancer for all anatomic sites combined were found in male and female Spanish-surnamed residents of Los Angeles County when compared to other whites. These Mexican-Americans were at lower risk for cancer of the buccal cavity, colon, rectum, larynx, lung, breast, bladder, prostate, and testis, and were at higher risk for cancer of the stomach, gallbladder, liver, and cervix. Immigrant Mexican-Americans had incidence rates most divergent from other whites, whereas indigenous Mexican-Americans had rates between the other two groups. The cancer pattern in Mexican-Americans was generally similar to that in American Indians. These data were most consistent with environmental variations in cause.

Lung cancer and air pollution in southcentral Los Angeles County.

An increased rate of lung cancer has been consistently observed from 1968-1972 among males in southcentral Los Angeles. This excess risk occurs across several social classes and occupational categories. No differential excess of oral cavity, pancreatic, laryngeal and bladder cancer was observed in the same area, lessening the possibility that regional variations in smoking habits accounted for the excess lung cancer. Air sampling has indicated an excess of certain polynuclear aromatic hydrocarbons (PAH) in southcentral Los Angeles. There was a correlation between the geographic distribution of lung cancer cases and the general location of industries which have emitted these PAH. A case-controlled study of smoking, occupational and residential history in the southcentral area is underway.