RESUMO
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.
Assuntos
Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto/imunologia , Imunossupressores/uso terapêutico , Transplante das Ilhotas Pancreáticas/imunologia , Isoantígenos/imunologia , Transfusão de Linfócitos/métodos , Linfócitos T Reguladores/imunologia , Animais , Quimioterapia Combinada , Rejeição de Enxerto/imunologia , Projetos Piloto , PrimatasRESUMO
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.
Assuntos
Linfócitos B/imunologia , Tolerância Imunológica , Antígenos Comuns de Leucócito/imunologia , Proteínas de Membrana/fisiologia , Animais , Receptor Celular 1 do Vírus da Hepatite A , Camundongos , Camundongos EndogâmicosRESUMO
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.
Assuntos
Neoplasias/epidemiologia , Adolescente , Adulto , Idoso , Neoplasias da Mama/epidemiologia , California , Criança , Pré-Escolar , Emigração e Imigração , Feminino , Humanos , Lactente , Recém-Nascido , Neoplasias Pulmonares/epidemiologia , Masculino , México/etnologia , Pessoa de Meia-Idade , Risco , Neoplasias da Bexiga Urinária/epidemiologia , Neoplasias do Colo do Útero/epidemiologiaAssuntos
Neoplasias/epidemiologia , Fatores Etários , Idoso , Ordem de Nascimento , Neoplasias da Mama/genética , California , Neoplasias do Colo/genética , Complicações do Diabetes , Diabetes Mellitus/genética , Meio Ambiente , Características da Família , Feminino , Cardiopatias/complicações , Cardiopatias/genética , Humanos , Hipersensibilidade/complicações , Hipersensibilidade/genética , Masculino , Pais , Neoplasias da Próstata/complicações , Estudos Retrospectivos , Fatores Sexuais , Neoplasias Cutâneas/genética , Inquéritos e QuestionáriosRESUMO
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.
RESUMO
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.