RESUMEN
This study analyzed in vivo antiviral cellular immune reactions in the Shope rabbit papilloma-carcinoma model. Antigens studied in experimentally infected domestic rabbits were cottontail rabbit papillomavirus particles produced with the athymic (nu/nu) mouse xenograft system and bacterial fusion proteins containing the major or minor capsid protein. Recall reactions to antigens were tested by classic intracutaneous tests. Positive reactions had a biphasic course. Histopathology of skin test biopsy specimens showed infiltrating polymorphonuclear cells during the early stages. Later they were replaced by predominantly perivascular infiltrates composed of mononuclear cells. Time course of swelling and infiltrates resembled a delayed-type hypersensitivity reaction. Ten of 11 regressor rabbits (p = 0.00006) and 10 of 20 progressors (p = 0.009) had positive skin tests with intact and/or denaturated virus particles and individual capsid proteins also could elicit specific skin reactions. Skin reactivity to the cottontail rabbit papillomavirus particles was also greater (p = 0.042) in regressor rabbits (8 of 11) when compared to progressors (7 of 20). Recall reactions remained detectable at post-regression times, ranging from several months up to more than 2 years. We conclude that specific skin reactions against the cottontail rabbit papillomavirus in infected domestic rabbits exist, and are strongly positive to intact particles of this papillomavirus in animals (regressors) clinically free of disease.
Asunto(s)
Antígenos Virales/administración & dosificación , Papillomavirus del Conejo de Rabo Blanco/inmunología , Pruebas Cutáneas , Infecciones Tumorales por Virus/inmunología , Animales , Antígenos Virales/genética , Biopsia , Modelos Animales de Enfermedad , Inmunidad , Proteínas/análisis , Conejos , Piel/patología , Neoplasias Cutáneas/inmunologíaRESUMEN
The purpose of the study was to investigate the cytokine gene expression patterns and immunohistochemical characteristics of genitoanal warts in order to obtain a clue as to the immunological mechanisms possibly relevant for wart regression or persistence. We analysed surgically removed warts from 11 patients, 2 of whom were immunosuppressed. Lesions of five of the nine otherwise healthy individuals were additionally treated with intralesional interferon-gamma (IFN gamma) prior to surgery. Invasion of CD4+ T cells into the papillomas and HLA-DR and ICAM-1 expression on keratinocytes were found in two otherwise healthy patients and were intensified by intralesional IFN gamma in four of five patients. The mRNA expression patterns in seven of eight non-recurrent warts were compatible with a predominant TH1 or mixed TH1/TH2 cytokine profile. In contrast, in recalcitrant warts of three patients (one healthy, two immunocompromised) histological signs of immunore-activity and TH1-like cytokine mRNA expression were not detected. In recurrent warts of a renal transplant patient, IL-4 and IL-5 mRNA expression was repeatedly found suggesting a predominant TH2 response. In conclusion, immunoreactivity to genitoanal warts such as T-cell infiltration, HLA-DR and ICAM-1 expression was associated with a predominant TH1 or mixed TH1/ TH2 cytokine mRNA expression profile.
Asunto(s)
Linfocitos T CD4-Positivos/inmunología , Condiloma Acuminado/inmunología , Citocinas/biosíntesis , Antígenos HLA-DR/biosíntesis , Molécula 1 de Adhesión Intercelular/biosíntesis , Interferón gamma/farmacología , Adulto , Linfocitos T CD8-positivos/inmunología , Condiloma Acuminado/genética , Condiloma Acuminado/terapia , Citocinas/genética , Regulación de la Expresión Génica , Humanos , Interferón gamma/uso terapéutico , Interferones/biosíntesis , Interferones/genética , Interleucinas/biosíntesis , Interleucinas/genética , Queratinocitos/metabolismo , Masculino , Persona de Mediana Edad , ARN Mensajero/genética , ARN Mensajero/metabolismo , Células TH1/inmunología , Células Th2/inmunología , Factores de Crecimiento Transformadores/biosíntesis , Factores de Crecimiento Transformadores/genética , Factor de Necrosis Tumoral alfa/biosíntesis , Factor de Necrosis Tumoral alfa/genéticaRESUMEN
The etiology of verruciform xanthoma, a rare lesion that usually occurs in the oral mucosa, is unknown. A viral etiology has been speculated since extraoral lesions usually occur in the genitalia. We present, to the best of our knowledge, the first reported case of verruciform xanthoma in an immunocompromised patient with chronic graft versus host disease. Immunohistochemical studies showed a few Ham 56 (a macrophage marker) positive foam cells, both in the dermis and within the epidermis, supporting a role for an epidermal process in production of the foam cells. Staining for human papillomavirus protein (HPV) showed reactivity of some of the nuclei in the dermal histiocytes, but in situ hybridization for HPV types 6/11, 16/18, and 31, 33 was negative. These results support an epidermal process as the stimulus for the foam cell formation but fail to demonstrate HPV as the cause.