CD4 T cell subsets in the mucosa are CD28+Ki-67−HLA-DR−CD69+ but show differential infection based on α4β7 receptor expression during acute SIV infection
Article first published online: 16 OCT 2009
© 2009 John Wiley & Sons A/S. No claim to original US government works
Journal of Medical Primatology
Special Issue: 26th Annual Symposium of Nonhuman Primate Models for AIDS
Volume 38, Issue Supplement s1, pages 24–31, October 2009
How to Cite
Kader, M., Bixler, S., Roederer, M., Veazey, R. and Mattapallil, J.J. (2009), CD4 T cell subsets in the mucosa are CD28+Ki-67−HLA-DR−CD69+ but show differential infection based on α4β7 receptor expression during acute SIV infection. Journal of Medical Primatology, 38: 24–31. doi: 10.1111/j.1600-0684.2009.00372.x
- Issue published online: 16 OCT 2009
- Article first published online: 16 OCT 2009
- Accepted 1 July 2009.
Background CD4 T cell depletion in the mucosa has been well documented during acute HIV and SIV infections. The demonstration the HIV/SIVcan use the α4β7 receptor for viral entry suggests that these viruses selectively target CD4 T cells in the mucosa that express high levels of α4β7 receptor.
Methods Mucosal samples obtained from SIV infected rhesus macaques during the early phase of infection were used for immunophenotypic analysis. CD4 T cell subsets were sorted based on the expression of β7 and CD95 to quantify the level of SIV infection in different subsets of CD4 T cells. Changes in IL-17, IL-21, IL-23 and TGFβ mRNA expression was determined using Taqman PCR.
Results CD4 T cells in the mucosa were found to harbor two major population of cells; -25% of CD4 T cells expressed the α4+β7hi phenotype, whereas the rest of the 75% expressed an α4+β7int phenotype. Both the subsets were predominantly CD28+Ki-67-HLA-DR- but CD69+, and expressed detectable levels of CCR5 on their surface. Interestingly, however, α4+β7hiCD4 T cells were found to harbor more SIV than the α4+β7int subsets at day 10 pi. Early infection was associated with a dramatic increase in the expression of IL-17, and IL-17 promoting cytokines IL-21, IL-23, and TGFβ that stayed high even after the loss of mucosal CD4 T cells.
Conclusions Our results suggest that the differential expression of the α4β7 receptor contributes to the differences in the extent of infection in CD4 T cell subsets in the mucosa. Early infection is associated dysregulation of the IL-17 network in mucosal tissues involves other non-Th-17 cells that likely contributes to the pro-inflammatory environment in the mucosa during acute stages of SIV infection.