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Compartmentalization of simian immunodeficiency virus replication within secondary lymphoid tissues of rhesus macaques is linked to disease stage and inversely related to localization of virus-specific CTL.
Connick, Elizabeth; Folkvord, Joy M; Lind, Katherine T; Rakasz, Eva G; Miles, Brodie; Wilson, Nancy A; Santiago, Mario L; Schmitt, Kimberly; Stephens, Edward B; Kim, Hyeon O; Wagstaff, Reece; Li, Shengbin; Abdelaal, Hadia M; Kemp, Nathan; Watkins, David I; MaWhinney, Samantha; Skinner, Pamela J.
Afiliación
  • Connick E; Division of Infectious Diseases, Department of Medicine, University of Colorado Anschutz Medical Campus, Denver, CO 80045; liz.connick@ucdenver.edu.
  • Folkvord JM; Division of Infectious Diseases, Department of Medicine, University of Colorado Anschutz Medical Campus, Denver, CO 80045;
  • Lind KT; Division of Infectious Diseases, Department of Medicine, University of Colorado Anschutz Medical Campus, Denver, CO 80045;
  • Rakasz EG; Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI 53715;
  • Miles B; Division of Infectious Diseases, Department of Medicine, University of Colorado Anschutz Medical Campus, Denver, CO 80045;
  • Wilson NA; Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI 53715;
  • Santiago ML; Division of Infectious Diseases, Department of Medicine, University of Colorado Anschutz Medical Campus, Denver, CO 80045;
  • Schmitt K; Department of Microbiology, Molecular Genetics, and Immunology, University of Kansas Medical Center, Kansas City, KS 66160;
  • Stephens EB; Department of Microbiology, Molecular Genetics, and Immunology, University of Kansas Medical Center, Kansas City, KS 66160;
  • Kim HO; Department of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, MN;
  • Wagstaff R; Department of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, MN;
  • Li S; Department of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, MN;
  • Abdelaal HM; Department of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, MN; Department of Microbiology and Immunology, Zagazig University, Zagazig, Egypt 44519; and.
  • Kemp N; Department of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, MN;
  • Watkins DI; Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI 53715;
  • MaWhinney S; Department of Biostatistics and Informatics, University of Colorado Denver, Aurora, CO 80045.
  • Skinner PJ; Department of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, MN;
J Immunol ; 193(11): 5613-25, 2014 Dec 01.
Article en En | MEDLINE | ID: mdl-25362178
We previously demonstrated that HIV replication is concentrated in lymph node B cell follicles during chronic infection and that HIV-specific CTL fail to accumulate in large numbers at those sites. It is unknown whether these observations can be generalized to other secondary lymphoid tissues or whether virus compartmentalization occurs in the absence of CTL. We evaluated these questions in SIVmac239-infected rhesus macaques by quantifying SIV RNA(+) cells and SIV-specific CTL in situ in spleen, lymph nodes, and intestinal tissues obtained at several stages of infection. During chronic asymptomatic infection prior to simian AIDS, SIV-producing cells were more concentrated in follicular (F) compared with extrafollicular (EF) regions of secondary lymphoid tissues. At day 14 of infection, when CTL have minimal impact on virus replication, there was no compartmentalization of SIV-producing cells. Virus compartmentalization was diminished in animals with simian AIDS, which often have low-frequency CTL responses. SIV-specific CTL were consistently more concentrated within EF regions of lymph node and spleen in chronically infected animals regardless of epitope specificity. Frequencies of SIV-specific CTL within F and EF compartments predicted SIV RNA(+) cells within these compartments in a mixed model. Few SIV-specific CTL expressed the F homing molecule CXCR5 in the absence of the EF retention molecule CCR7, possibly accounting for the paucity of F CTL. These findings bolster the hypothesis that B cell follicles are immune privileged sites and suggest that strategies to augment CTL in B cell follicles could lead to improved viral control and possibly a functional cure for HIV infection.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Bazo / Linfocitos T Citotóxicos / Síndrome de Inmunodeficiencia Adquirida del Simio / Virus de la Inmunodeficiencia de los Simios / Ganglios Linfáticos Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: J Immunol Año: 2014 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Bazo / Linfocitos T Citotóxicos / Síndrome de Inmunodeficiencia Adquirida del Simio / Virus de la Inmunodeficiencia de los Simios / Ganglios Linfáticos Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: J Immunol Año: 2014 Tipo del documento: Article Pais de publicación: Estados Unidos