Activation‐induced marker assays for identification of Trypanosoma cruzi‐specific CD4 or CD8 T cells in chronic Chagas disease patients

• Published in: Immunology Vol. 169; no. 2; pp. 185 - 203
• Main Authors: Ferragut, Fátima, Cruz, Karen M., Gallardo, Juan P., Fernández, Marisa, Hernández Vasquez, Yolanda, Gómez, Karina A.
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01-06-2023
• Subjects: activation‐induced markers; Adaptive immunity; Antigens; Assaying; B7-H1 Antigen; CCR7 protein; CD11a antigen; CD137 antigen; CD25 antigen; CD38 antigen; CD4; CD4 antigen; CD40 Ligand; CD40L protein; CD45RA antigen; CD49d antigen; CD69 antigen; CD8; CD8 antigen; CD8-Positive T-Lymphocytes; Chagas disease; Chagas Disease - diagnosis; chronic Chagas disease; human; Humans; Immune response; Lymphocytes; Lymphocytes T; Parasites; PD-L1 protein; Phenotypes; Protozoa; Stimulation; Surface markers; T cells; T. cruzi; Trypanosoma cruzi; Tumor necrosis factor; Vector-borne diseases; CD4; CD8; T. cruzi; T cells; chronic Chagas disease; human; activation-induced markers
• ISSN: 0019-2805; 1365-2567
• DOI: 10.1111/imm.13622

Antigen‐specific T cells are central to the adaptive immune response against T. cruzi infection and underpin the efficacy of on‐going vaccine strategies. In this context, the present study focuses on T‐cell assays that define the parasite‐specificity on the basis of upregulation of TCR stimulation‐induced surface markers. For this purpose, we tested different dual marker combinations (OX40, CD25, CD40L, CD137, CD69, PD‐L1, CD11a, CD49d, HLA‐DR, CD38) to reliably identify activated CD4+ and CD8+ T‐cell populations from PBMCs of chronic Chagas disease (CCD) patients after 12 or 24 h of stimulation with T. cruzi lysate. Results demonstrated that activation‐induced markers (AIM) assays combining the expression of OX40, CD25, CD40L, CD137, CD69 and/or PD‐L1 surface markers are efficient at detecting T. cruzi‐specific CD4+ T cells in CCD patients, in comparison to non‐infected donors, after both stimulation times. For CD8+ T cells, only PD‐L1/OX40 after 24 h of antigen exposure resulted to be useful to track a parasite‐specific response. We also demonstrated that the agnostic activation is mediated by different T. cruzi strains, such as Dm28c, CL Brener or Sylvio. Additionally, we successfully used this approach to identify the phenotype of activated T lymphocytes based on the expression of CD45RA and CCR7. Overall, our results show that different combinations of AIM markers represent an effective and simple tool for the detection of T. cruzi‐specific CD4+ and CD8+ T cells.
Activation‐induced markers (AIM) assay is useful to identify T. cruzi‐specific T cells in chronic Chagas disease patients. Several dual AIM markers designate CD4+ T‐cell activation, while only PD‐L1/OX40 identifies parasite‐specific CD8+ T lymphocytes. AIM assay allows the detection of T‐cell agnostic activation mediated by different T. cruzi strains, such as Dm28c, CL Brener or Sylvio.