Understanding follicular CD8 T cells during SIV infection


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A representative confocal image of follicular cells from 1 chronically SIV-infected animal. Germinal centres (GC) were defined by CD20+Ki67+ coexpression, and CD4+ (CD3+CD4+) and CD8+ (CD3+CD4–) T cells were quantified within each GC. Scale bar: 400 μm. (Source Ferrando-Martinez et al., 2018)

A representative confocal image of follicular cells from 1 chronically SIV-infected animal. Germinal centres (GC) were defined by CD20+Ki67+ coexpression, and CD4+ (CD3+CD4+) and CD8+ (CD3+CD4–) T cells were quantified within each GC. Scale bar: 400 μm. (Source Ferrando-Martinez et al., 2018)

CD8 T cells have been shown to be one of the main cellular mediators of HIV/SIV control. One of the major sites of HIV/SIV viral replication and persistence is lymph node. Understanding the dynamics of CD8 T cell anti-HIV immunity in the lymph node could aid in the development of future cure strategies.

Ferrando-Martinez et al., showed that  SIV-specific follicular (f)CD8 T cells are observed in both intact and disorganised lymph node follicles, and accumulate during chronic infection. SIV-specific fCD8 T cells did not have superior cytokine co-expression of IFN-γ, TNF and MIP-α capacity compared with non-fCD8 T cells. However, researchers observed significantly higher expression of granzyme (Grz) A, GrzB and perforin, as well increased cytotoxic activity of SIV-specific fCD8 compared with non-fCD8 T cells detected in the lymph node.

Researchers hypothesised that increased fCD8 T cells could be due to high viral replication, as CD8 T cells have been shown to be the main mediators of viral control in. To their surprise fCDC8 T cells were not preferentially colocalised with SIV-RNA+ cells using both confocal microscopy and histocytometry. Suggestin that though SIV replication is necessary for fCD8 accumulation, it may not be sufficient  to induce T cell trafficking. Using an Africa green monkey*- SIV infection models, researchers showed  that activation of cells plays an important role in fCD8 T cells trafficking. Additionally, this activation was also associated with increased proportions of CXCL10 expressing monocytes. Majority of CD8 T cells observed in the lymph node expressed high levels of CXCR3, the receptor for CXCL10. This suggest a potential mechanised of CXCL10-CXCR3 mediated attraction of fCD8 T cells.

In summary, this results validated the use of non-human primate models to study the  dynamics of fCD8 T cells in the lymph node during SIV infection. Additionally, they demonstrated a potential role of activation and inflammation in accumulation of cytotoxic SIV-specific fCD8 T cells. Justifying the exploration of fCD8 T cells as one of the avenues for achieving HIV cure.

*African Green Monkeys  have very low activation in the lymph node

Journal Article: Ferrando-Martinez et al., 2018. Accumulation of follicular CD8+ T cells in pathogenic SIV infection. Journal of Clinical Investigation.

 

Article by Cheleka AM Mpande

 
 
 
 
 
 
International Union of Immunological SocietiesUniversity of South AfricaInstitute of Infectious Disease and Molecular MedicineScience Education PrizesElizabeth Glazer Pediatric Aids Foundation