RESUMO
Coinfection with human T-cell lymphotropic virus type 2 (HTLV-2) and human immunodeficiency virus type 1 (HIV-1) has been reported to have either a slowed disease course or to have no effect on progression to AIDS. In this study, we generated a coinfection animal model and investigated whether HTLV-2 could persistently infect macaques, induce a T-cell response, and impact simian immunodeficiency virus SIV(mac251)-induced disease. We found that inoculation of irradiated HTLV-2-infected T cells into Indian rhesus macaques elicited humoral and T-cell responses to HTLV-2 antigens at both systemic and mucosal sites. Low levels of HTLV-2 provirus DNA were detected in the blood, lymphoid tissues, and gastrointestinal tracts of infected animals. Exposure of HTLV-2-infected or naïve macaques to SIV(mac251) demonstrated comparable levels of SIV(mac251) viral replication, similar rates of mucosal and peripheral CD4(+) T-cell loss, and increased T-cell proliferation. Additionally, neither the magnitude nor the functional capacity of the SIV-specific T-cell-mediated immune response was different in HTLV-2/SIV(mac251) coinfected animals versus SIV(mac251) singly infected controls. Thus, HTLV-2 targets mucosal sites, persists, and importantly does not exacerbate SIV(mac251) infection. These data provide the impetus for the development of an attenuated HTLV-2-based vectored vaccine for HIV-1; this approach could elicit persistent mucosal immunity that may prevent HIV-1/SIV(mac251) infection.
Assuntos
Infecções por HTLV-II/imunologia , Vírus Linfotrópico T Tipo 2 Humano/imunologia , Macaca mulatta/virologia , Vírus da Imunodeficiência Símia/imunologia , Animais , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/virologia , Células Dendríticas/imunologia , Células Dendríticas/virologia , Genoma Viral , Infecções por HIV/imunologia , HIV-1/imunologia , Humanos , Imunidade/imunologia , Mucosa Intestinal/imunologia , Mucosa Intestinal/virologia , Ativação Linfocitária/imunologia , Tecido Linfoide/imunologia , Tecido Linfoide/virologia , Carga ViralRESUMO
In response to a call for revision of the current procedures for involuntary treatment in Massachusetts, this commentary explores the ethics basis for such institutional reform. In the decades since the landmark Rogers v. Commissioner decision of 1983, the ethics foundation for forensic psychiatry has evolved from a purist approach that prioritized legal values above therapeutic ones. Building on systemic approaches by Gutheil et al. and Ciccone and Clements, Candilis and Martinez, for example, have argued that a robust professional ethic requires moving beyond the strict role theory of the adversarial system to consider broader approaches that integrate multiple perspectives: the ultimate goal is protection of vulnerable people and ideas. In this commentary, we suggest that the current system for involuntary treatment does not protect the vulnerable people it ought to serve, failing the neglected goal of social justice.