Activation of T regulatory cells in Type II Immune Responses

Monitoring lymphocyte subset changes in renal transplant recipients (RT) may allow direct evaluation of transplant tolerance and possible tailoring of immunosuppression to enhance quality of life and decrease risk of infection or malignancy. We examined changes in subsets of CD4+ T cells, CD4+CD25+CD127lo T regulatory cells (Treg), and B cells of patients on dialysis (ESKD) and renal graft recipients of varying lengths, and compared them to healthy volunteers. Demonstrating the heterogeneity of Treg, Miyara et al. (2009) have identified five populations (Pop) within CD4+ T cells based on CD45RA, CD25 and Foxp3 expression. Pop I, II and III are Treg, where Pop I is naive (CD45RA+Foxp3+), Pop II are activated (CD45RA-Foxp3hi), and Pop III are cytokine secreting (CD45RA-Foxp3+) which includes activated effector T cells. Pop IV and V are T cells, where Pop IV are activated T cells (CD45RA-Foxp3-) and Pop V are naïve (CD45RA+Foxp3-) T cells. In this project, we examined three Populations of Treg (Pop I-III) within CD4+CD25+CD127lo Treg, and Pop IV and V within CD4+ T cells. To characterise these subpopulations, we examined chemokine receptor expression (CXCR3, CCR4, CCR6, CCR7) to identify T helper (Th-like) phenotypes. We also examined Treg activation and suppression-related molecules (CD39, Class II MHC, and PD-1) within each subpopulation. We further examined for changes in B cell subsets. We found RT had lower lymphocyte counts, Treg, and B cells compared to HV. RT had fewer Treg subpopulations expressing CXCR3 or CCR6, and a higher proportion of Th2-like Treg in comparison to HV. We found no differences in Treg activation and suppression-related molecules. Within B cells, switched memory B cells and plasmablasts were higher in RT than HV. RT had a significantly higher ratio of Treg to B cells, which may demonstrate increased suppression in RT. Monitoring lymphocyte subpopulations of renal graft recipients showed important differences which need to be further investigated to determine their relevance to transplant tolerance. In animal studies, we aimed to explore a pathway of activation of naive rat Treg to Th2-like Treg using a two-step activation method. We examined this pathway in 3 strains of rats (Lewis, DA and PVG). Naive rat Treg were cultured with rIL-4 and specific antigen for 4 days, then re-cultured with rIL-5 and specific antigen for 3 days. Phenotypical changes were characterised by flow cytometry and droplet digital polymerase chain reaction.

Grantor dc:publisher

UNSW, Sydney

Year dc:date

2024

Author dc:creator

• Rakesh, Prateek

• T regulatory cell
• Renal transplant
• Kidney transplant
• Immune monitoring
• CD4+CD25+ T regulatory cells
• Activated Regulatory cells
• B cell subsets
• Th2-like Tregs
• anzsrc-for: 3204 Immunology
• anzsrc-for: 320408 Transplantation immunology

Statement dc:rights

• open access
• CC BY 4.0
• free_to_read

Licence

• https://purl.org/coar/access_right/c_abf2
• https://creativecommons.org/licenses/by/4.0/

Language dc:language

en

Identifier

https://doi.org/10.26190/unsworks/30750

OAI identifier oai:identifier

oai:unsworks.library.unsw.edu.au:1959.4/103749