Whole M.tb inherently induce highly differentiated T cells compared to H56 vaccination


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mycobacterium tuberculosis

Mycobacterium tuberculosis (Public Health Image Library, CDC, Image ID:16881 )

CD4 T cells, particularly those capable of producing IFN-γ have been shown to play an essential role in immunity against Mycobacterium tuberculosis (M.tb) infection and diseases. In spite of this, strong CD4 T cell IFN-γ responses induced by natural infection or current (and experimental) vaccines are unable to induce consistent protection against tuberculosis (TB). Highlighting the need for an improved understanding of T cell responses beyond cytokine function.

Lindenstrøm et al., researchers from Denmark and USA, aimed to compare functional, phenotypic and protective attributes of long term immunity induced by either M.tb-infection or H56/CAF01 vaccination (termed as H56 –memory). Lindenstrøm et al. utilised a “latent” M.tb infection mouse model (termed as M.tb-memory), where mice were infected with a low aerosol dose of M.tb (Erdmann strain) followed by a 12-week Isoniacid/Rifabutin (INH/RIF) treatment . INH/RIF treatment in M.tb-memory miceresulted in uncultivable bacteria in most mice up to 72 weeks post-treatment.

Using an aerosol M.tb challenge model, Lindenstrøm et al. demonstrated improved protection against M.tb challenge in H56-memory mice compared to M.tb-memory and control mice. Phenotypic characterisation of ESAT6-specific (sp) CD4 T cells in the lungs of M.tb challenged mice, showed higher expression levels of KLRG1, late T cell differentiation marker, in M.tb-memory mice than H56-memory mice. Additionally, ESAT-6-sp CD4 T cells from M.tb-memory and control mice were predominantly IFN-γ±TNF±, whereas ESAT-6-sp CD4 T cells from H56-memory mice were predominantly  TNF–α+IL2±IFN-γ± with a significantly high expression of IL-2, a function absent in M.tb-memory and control mice.

Lindenstrøm et al. utilised a T cell co-transfer model, to compare the lung homing capacity of T cells from M.tb-memory and H56-memory mice. Briefly, ESAT-6-sp CD4 T cells from M.tb- and H56-memory were transferred at 1:1 ratio to recipient mice. This experiment demonstrated superior lung homing capacity of ESAT-6-sp CD4 T cells from H56-memory mice compared to M.tb-memory mice.

This research highlights the role antigen: whole cell (M.tb) vs fusion protein with adjuvant (H56) and/or method: aerosol (M.tb) vs vaccination (H56) plays in T cell differentiation. Where priming a memory response with H56 vaccination results in quiescent less differentiated, “protective” T cell responses that have superior lung parenchyma homing ability compared to whole mycobacterium (M.tb and BCG) priming.

Journal Article: Lindenstrøm et al. 2017. T Cells Primed by Live Mycobacteria Versus a Tuberculosis Subunit Vaccine Exhibit Distinct Functional Properties. EBioMedicine.

 

Article by Cheleka AM Mpande

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