Toxoplasma gondii: CD8 T Cells Cry for CD4 Help

Abstract

Toxoplasma gondii , an apicomplexan parasite, is a pathogenic protozoan that can infect the central nervous system. In pregnant women, infection can result in congenital problems of the fetus, while in immunocompromised individual it can lead to severe neurological consequences. Although CD8 T cells play an important effector role in controlling the chronic infection, their maintenance is dependent on the critical help provided by CD4 T cells. In a recent study, we demonstrated that reactivation of the infection in chronically infected host is a consequence of CD8 T dysfunction caused by CD4 T cell exhaustion. Furthermore, treatment of chronically infected host with antigen-specific non-exhausted CD4 T cells can restore CD8 T cell functionality and prevent reactivation of the latent infection. The exhaustion status of CD4 T cells is mediated by the increased expression of the transcription factor BLIMP-1, and deletion of this molecule led to the restoration of CD4 T cell function, reversal of CD8 exhaustion and prevention of reactivation of the latent infection. In a recent study from our laboratory, we also observed an increased expression of miR146a levels by CD4 T cells from the chronically infected animals. Recent reports have demonstrated that microRNAs (especially miR146a) has a strong impact on the immune system of T . gondii infected host. Whether these molecules have any role in the BLIMP-1 up-regulation and dysfunctionality of these cells needs to be investigated.

Protective immunity induced by CpG ODN‐adjuvanted virus‐like particles containing Toxoplasma gondii proteins

“…Accordingly, it was reported that transferring CD8 + T cells into immunodeficient mice resulted in the elimination of T gondii cysts in the brains 33 . CD4 + T‐cell exhaustion was documented to disrupt the functionality of CD8 + T cells and ultimately lead to recrudescent toxoplasmosis 34 . Consistent with these reports, fewer cyst counts were detected in the brains of mice immunized with TG146 VLP + CpG vaccine, whose CD8 + T‐cell populations were much greater than those induced by TG146 VLPs alone.…”

Diagnostic significance of C-reactive protein and hematological parameters in acute toxoplasmosis

“…The lymphocytes role in T. gondii infection is in restriction of parasite replication during the chronic phase. Amongst the adaptive immune subsets, CD8 T lymphocytes are the primary effector cells while CD4 T cells play an essential helper function to maintain long-term immunity (Khan et al 2019 ). The action of lymphocytes in T. gondii infection starts with its activation by macrophages and dendritic cells, followed by induction of Th1 cells and antigen-specific killer CD8 T cells.…”

Pathophysiology of ocular toxoplasmosis: Facts and open questions

“…gondii infection, such as DCs, macrophages, CD8 + and CD4 + lympocytes, granulocytes, and NK cells. In particular, CD4 + T h 1 cells, activated through interleukin 12 (IL12) stimulation from antigen-presenting cells (APCs), induce a robust CD8 + T cell effector immunity, these cells being an important source of IFNγ and also exhibiting cytotoxic activity against infected targets [ 51 , 52 ]. These principles of systemic immunity to T .…”