We recently demonstrated that the intestinal mucosa is the major site of CD4+ T cell depletion in acute SIV infection Severe depletion of CD4+ T cells occurs rapidly (within days), selectively, and consistently within the gastrointestinal tract following intravenous infection with standard pathogenic molecular clones of SIV No significant changes in single-positive CD4+ T cells can be detected in the blood, peripheral lymph nodes, or spleen of these same animals at these same postinoculation intervals To determine whether this phenomenon occurs following SIV infection by other routes of inoculation, we have since tested six rectally inoculated macaques and found that comparable early CD4+ T cell depletion also occurs following a mucosal route of inoculation Profound and rapid intestinal CD4 depletion occurred within 14 days postinoculation in all six of these animals We have also expanded our analysis to include other mucosal sites (vagina, rectum, lung) a nd h ave found that rapid and profound CD4+ T cell depletion occurs in these sites as well Our data demonstrates that rapid CD4 depletion occurs within days of SIV infection in all mucosal tissues and also that it occurs independently of the site or route of the initial inoculation These results show that SIV infection is predominantly a disease of the mucosal immune system

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Primate Research Center Grants (P51)
Project #
5P51RR000168-38
Application #
6116532
Study Section
Project Start
1999-05-01
Project End
2000-04-30
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
38
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Harvard University
Department
Type
DUNS #
082359691
City
Boston
State
MA
Country
United States
Zip Code
02115
Shang, L; Smith, A J; Reilly, C S et al. (2018) Vaccine-modified NF-kB and GR signaling in cervicovaginal epithelium correlates with protection. Mucosal Immunol 11:512-522
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Isakova, Irina A; Baker, Kate C; Dufour, Jason et al. (2017) Mesenchymal Stem Cells Yield Transient Improvements in Motor Function in an Infant Rhesus Macaque with Severe Early-Onset Krabbe Disease. Stem Cells Transl Med 6:99-109
Termini, James M; Church, Elizabeth S; Silver, Zachary A et al. (2017) Human Immunodeficiency Virus and Simian Immunodeficiency Virus Maintain High Levels of Infectivity in the Complete Absence of Mucin-Type O-Glycosylation. J Virol 91:

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