Compartmentalization of SIV Replication Within Secondary Lymphoid Tissues of Rhesus Macaques is Linked to Disease Stage and Inversely Related to Localization of Virus-Specific CTL12

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• Alternative Title:
  J Immunol
• Personal Author:
  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.
• Description:
  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.
• Subjects:
  Animals Antigens, Viral Article Cell Movement Cells, Cultured Disease Progression Lymph Nodes Macaca Mulatta Receptors, CCR7 Receptors, CXCR5 RNA, Viral Simian Acquired Immunodeficiency Syndrome Simian Immunodeficiency Virus Spleen T-Lymphocytes, Cytotoxic Virus Replication

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• Source:
  J Immunol. 193(11):5613-5625
• Pubmed ID:
  25362178
• Pubmed Central ID:
  PMC4239212
• Document Type:
  Journal Article
• Funding:
  R01 AI090795/NIAID NIH HHS/National Institute of Allergy and Infectious Diseases Extramural Activities/United States ; P51 RR000167/NCRR NIH HHS/National Center for Research Resources/United States ; HHSN272201300006C/NIAID NIH HHS/National Institute of Allergy and Infectious Diseases Extramural Activities/United States ; U24 AI126683/NIAID NIH HHS/National Institute of Allergy and Infectious Diseases Extramural Activities/United States ; R01 AI096966/NIAID NIH HHS/National Institute of Allergy and Infectious Diseases Extramural Activities/United States ; P51RR000167/RR/NCRR NIH HHS/United States ; R56 AI080418/NIAID NIH HHS/National Institute of Allergy and Infectious Diseases Extramural Activities/United States ; T32 AI007447/NIAID NIH HHS/National Institute of Allergy and Infectious Diseases Extramural Activities/United States ; HHSN272200900037C/NIAID NIH HHS/National Institute of Allergy and Infectious Diseases Extramural Activities/United States ; R24 RR016001/NCRR NIH HHS/National Center for Research Resources/United States ; R56AI080418/AI/NIAID NIH HHS/United States ; R01AI090795/AI/NIAID NIH HHS/United States ; P51 OD011106/ODCDC CDC HHS/Office of the Director/United States ; P51OD011106/OD/NIH HHS/United States ; R01AI096966/AI/NIAID NIH HHS/United States ; HHSN272201300006C/NIAID NIH HHS/National Institute of Allergy and Infectious Diseases Extramural Activities/United States ; HHSN 2722000900037C/PHS HHS/United States
• Volume:
  193
• Issue:
  11
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:91c8ca0634933d51ba8d356cb7a1f667d3d23e754f76a2e23c0eebb3c0bc027c
• Download URL:
  https://stacks.cdc.gov/view/cdc/80570/cdc_80570_DS1.pdf
• File Type:
  [PDF - 2.71 MB ]