CD4+ T-cell loss and delayed expression of modulators of immune responses at mucosal sites of vaccinated macaques following SIVmac251 infection

M. Vaccari, A. Boasso, Z. M. Ma, V. Cecchinato, D. Venzon, M. N. Doster, W. P. Tsai, G. M. Shearer, D. Fuchs, B. K. Felber, G. N. Pavlakis, Chris J Miller, G. Franchini

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Systemic immunization of macaques with a combination of DNA-poxvirus-based vaccines confers protection from high level of both systemic and mucosal viral replication following rectal exposure to the pathogenic SIVmac251. Here we investigated early post-infection events in rectal and vaginal tissues, and found that the loss of CCR5+CD4+ T cells was equivalent in vaccinated and control macaques, despite a three logs reduction at mucosal sites of simian immunodeficiency virus (SIV) RNA in the vaccinated group. Even though a normal CD4+ T cell number is not reconstituted at mucosal sites in either group, vaccination appeared to confer a better preservation of the CD4+ CCR5+ T cells that replenish these sites. Analysis of rectal tissues RNA following challenge exposure demonstrated a decreased expression in vaccinated macaques of transforming growth factor-β, cytotoxic T lymphocyte antigen-4, FoxP3, and indoleamine 2,3-dioxygenase, an immune suppressive enzyme expressed by dendritic cells that converts tryptophan to kynurenine and limits T-cell responses. Accordingly, the ratio of kynurenine and tryptophan in the plasma was significantly reduced in the vaccinated animals respect to the controls. Thus, preexisting adaptive immune responses induced by these vaccine modalities, although they do not protect from CD4+ T-cell depletion, nevertheless, they contain SIVmac251 replication and delay expression of markers of T-cell activation and/or suppression at mucosal sites.

Original languageEnglish (US)
Pages (from-to)497-507
Number of pages11
JournalMucosal Immunology
Volume1
Issue number6
DOIs
StatePublished - 2008

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Mucosal Immunity
Macaca
T-Lymphocytes
Infection
Kynurenine
Tryptophan
Vaccines
CTLA-4 Antigen
RNA
Indoleamine-Pyrrole 2,3,-Dioxygenase
Poxviridae
Simian Immunodeficiency Virus
Transforming Growth Factors
Adaptive Immunity
Dendritic Cells
Immunization
Vaccination
Cell Count
DNA
Enzymes

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

CD4+ T-cell loss and delayed expression of modulators of immune responses at mucosal sites of vaccinated macaques following SIVmac251 infection. / Vaccari, M.; Boasso, A.; Ma, Z. M.; Cecchinato, V.; Venzon, D.; Doster, M. N.; Tsai, W. P.; Shearer, G. M.; Fuchs, D.; Felber, B. K.; Pavlakis, G. N.; Miller, Chris J; Franchini, G.

In: Mucosal Immunology, Vol. 1, No. 6, 2008, p. 497-507.

Research output: Contribution to journalArticle

Vaccari, M, Boasso, A, Ma, ZM, Cecchinato, V, Venzon, D, Doster, MN, Tsai, WP, Shearer, GM, Fuchs, D, Felber, BK, Pavlakis, GN, Miller, CJ & Franchini, G 2008, 'CD4+ T-cell loss and delayed expression of modulators of immune responses at mucosal sites of vaccinated macaques following SIVmac251 infection', Mucosal Immunology, vol. 1, no. 6, pp. 497-507. https://doi.org/10.1038/mi.2008.60
Vaccari, M. ; Boasso, A. ; Ma, Z. M. ; Cecchinato, V. ; Venzon, D. ; Doster, M. N. ; Tsai, W. P. ; Shearer, G. M. ; Fuchs, D. ; Felber, B. K. ; Pavlakis, G. N. ; Miller, Chris J ; Franchini, G. / CD4+ T-cell loss and delayed expression of modulators of immune responses at mucosal sites of vaccinated macaques following SIVmac251 infection. In: Mucosal Immunology. 2008 ; Vol. 1, No. 6. pp. 497-507.
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