CD4+ICOS+Foxp3+regulatory T cells: A Novel Sub-population Associated with Pathogenesis of Malaria

Abstract

The protective immune response and disease outcome are known to be counterbalanced by regulatory T cells. The role of naturally occurring regulatory cells CD4⁺CD25⁺Foxp3⁺ in malaria infection remains debatable. ICOS molecule has been demonstrated to play a role in the growth and function of regulatory T cells and helps T regulatory cells to produce more IL-10. This work investigates the role of ICOS-dependent regulatory CD4⁺ICOS⁺Foxp3⁺ T cells in resistance and susceptibility to the malaria parasite. Here, the expression of CD4⁺ICOS⁺ Foxp3 ⁺ T regulatory cells in lethal and non-lethal malaria parasite infection was examined. During lethal infection, CD4⁺ICOS⁺ T cells increase as the disease progress. Whereas, in non-lethal parasite infection, along with the reduction in parasitaemia after day 7 post-infection, ICOS expression was also decreases. In lethal parasitic infection, the frequency of CD4 ⁺ICOS⁺FoxP3⁺ T regulatory cells was substantially higher compared to the non-lethal parasitic infection. Moreover, there was noteworthy difference in the cytokine’s profiles of both lethal and non-lethal infections. In non-lethal infection, the expression of (IL-12) interlukin-12⁺ CD4⁺T cells was increases substantially, when compared to the lethal malaria infection. The relative frequency of IL-10⁺CD4⁺T cells was significantly higher in lethal parasite infection with subsequently high serum levels of IL-10 cytokines. Overall, these findings suggest that during lethal parasite infection, CD4⁺ICOS⁺Foxp3⁺ regulatory T cells induce an immunosuppressive environment in the host immune system, than enables the pathogen to sustain and enhances parasite survival.