Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Hall 4EF
It is increasingly well-recognized that donor-specific antibodies (DSA) play a significant role in the development of chronic rejection and fibrosis that contribute to late renal allograft loss. Thus, understanding the mechanisms responsible for DSA formation is necessary to improve long-term outcomes. T follicular helper (TFH) and regulatory (TFR) cells are distinct subsets of CD4+ T cells that are critical mediators of the humoral immune response. TFH and TFR cells function primarily within germinal centers (GC) of secondary lymphoid organs, rendering them elusive targets for immune monitoring in transplant recipients. Recent studies have identified circulating TFH (cTFH) cells that correlate with ongoing antibody responses after vaccination and in autoimmune disease, but little is known about the existence of cTFH cells during transplantation. To determine the kinetics and magnitude of circulating TFH and TFR (cTFR) cells during transplant, we utilized a major MHC mismatch BALB/c to B6 murine skin transplant model. Flow cytometric analysis of the peripheral blood revealed a 3-fold and 2-fold expansion in the frequency and absolute number of CD4+CXCR5+Foxp3– cTFH and Foxp3+ cTFR cells, respectively, 10 days after BALB/c skin transplantation as compared to naïve and syngeneic controls. Both circulating subsets expressed increased levels of Ki-67, reduced amounts of CXCR5 and ICOS, and no detectable Bcl-6 or PD-1 relative to their draining lymph node (dLN) counterparts. Interestingly, the majority of cTFH cells were CD44hi 10 days after transplant at the peak of the TFH response but reflected a more quiescent predominant CD44lo composition by day 14, indicating a detectable phenotypic shift in the cTFH cell pool that corresponded to peak anti-donor germinal center reactivity in the dLN. These graft-elicited changes also correlated with the initiation of anti-BALB/c IgG DSA generation. CD28 costimulation pathway blockade abrogated all components of the donor-reactive GC response, DSA formation, the observed expansion in cTFH and cTFR cells, and the increase in frequency of CD44hi cTFH cells at the peak of the alloimmune response. These data support continued investigations aimed to develop cTFH cells as a biomarker for the clinical assessment of humoral alloimmunity to guide DSA management for improvement of long-term kidney transplant outcomes.
CITATION INFORMATION: La Muraglia II G., Wagener M., Ford M., Badell R. Circulating T Follicular Helper Cells Expand Following Transplantation and Exhibit a CD44hi Phenotype That Correlates with Peak Germinal Center Alloreactivity Am J Transplant. 2017;17 (suppl 3).
To cite this abstract in AMA style:II GLaMuraglia, Wagener M, Ford M, Badell R. Circulating T Follicular Helper Cells Expand Following Transplantation and Exhibit a CD44hi Phenotype That Correlates with Peak Germinal Center Alloreactivity [abstract]. https://atcmeetingabstracts.com/abstract/circulating-t-follicular-helper-cells-expand-following-transplantation-and-exhibit-a-cd44hi-phenotype-that-correlates-with-peak-germinal-center-alloreactivity/. Accessed November 13, 2019.
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