Advances in Direct T-Cell Alloreactivity: Function, Avidity, Biophysics and Structure

Smith, Corey; Miles, John J.; Khanna, Rajiv

doi:10.1111/j.1600-6143.2011.03863.x

Cited by 27 publications

(26 citation statements)

References 132 publications

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“…Accelerated kinetic of rejection in animal that were previously grafted had been reported decades ago (18), and numerous examples of cross-reactivity of CD8 T cells between viral peptide and allogeneic HLA have been reported (19). We have also recently reported that an accumulation of TEMRA CD8 T cells in kidney transplant recipients with stable graft function is associated with an increased risk of kidney dysfunction (11).…”

Section: Discussionmentioning

confidence: 88%

Benefits of Using CD45RA and CD28 to Investigate CD8 Subsets in Kidney Transplant Recipients

Yap

Tilly

Giral

et al. 2016

American Journal of Transplantation

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The deleterious role of CD8 T cells in kidney graft outcome has regained interest over the years, and memory T cells are considered as one of the main hurdles to achieve transplantation success. Monitoring the CD8 immune response in transplant recipients involved a heterogeneous combination of markers, but the justification of their choice is rarely stated. Whereas the number of parameters is not an issue in phenotypic analysis, functional assays have to accommodate the cell number with the narrowing of the subset. The aim of the study was to investigate the similarities and differences of the subsets identified using three nomenclatures (CD45RA and CCR7/CD27/ CD28) in kidney transplant recipients with stable graft function. We found that all three nomenclatures can identify na€ ıve and effector memory (EM) rheumatoid arthritis T cell CD8 with similar features. Whereas CM CD8 could only be documented using CCR7 and CD45RA, the characteristics of EM CD8 will differ according to the nomenclature. We found that the use of the CD45RA and CD28 gives the benefit of examining two EM populations at early and late differentiation states. This systematic comparison provides a cohesive layout of the advantages of using these nomenclature strategies in kidney transplant recipients to guide the choice of their use.

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Section: Discussionmentioning

confidence: 88%

Benefits of Using CD45RA and CD28 to Investigate CD8 Subsets in Kidney Transplant Recipients

Yap

Tilly

Giral

et al. 2016

American Journal of Transplantation

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“…This affinity of the T-cell receptor for allogeneic MHC molecules can be higher than that for self-antigens. Heterologous immunity has been shown both in mice and in humans (Smith et al 2012). Homeostatic proliferation occurs in lymphopenic conditions (such as those caused by certain immunotherapies) and in the absence of an antigenic stimulus.…”

Section: Memory T Cellsmentioning

confidence: 99%

Effector Mechanisms of Rejection

Moreau

Varey

Anegón

et al. 2013

Cold Spring Harbor Perspectives in Medicine

142

136

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“…Memory T cells are recognized as a barrier to many immunomodulation strategies aimed at limiting alloreactive T cell responses (3). One reason is that microbe-elicited T cell memory can cross-react with allogeneic antigen and mediate graft rejection, a process termed allogeneic heterologous immunity (4, 5). In this scenario, memory CD8 + T cells that were primed with microbial antigen can recognize a unique cross-reactive allogeneic antigen.…”

Section: Introductionmentioning

confidence: 99%

Low-Affinity Memory CD8+ T Cells Mediate Robust Heterologous Immunity

Krummey

Martinez

Andargachew

et al. 2016

The Journal of Immunology

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Heterologous immunity is recognized as a significant barrier to transplant tolerance. While pathogen elicited memory T cells can have high or low affinity for cross-reactive allogeneic peptide:MHC, the role T cell receptor (TCR) affinity during heterologous immunity has not been explored. We established a model with which to investigate the impact of TCR priming affinity on memory T cell populations following a graft rechallenge. In contrast to high affinity priming, low affinity priming elicited fully differentiated memory T cells with a CD45RBhi status. High CD45RB status enabled robust secondary responses in vivo, as demonstrated by faster graft rejection kinetics and greater proliferative responses. CD45RB blockade prolonged graft survival in low affinity, but not high affinity, primed mice. Mechanistically, low affinity primed memory CD8+ T cells produced more IL-2 and significantly upregulated IL-2Rα expression during rechallenge. We found that CD45RBhi status was also a stable marker of priming affinity within polyclonal CD8+ T cell populations. Following high affinity rechallenge, low affinity primed CD45RBhi cells became CD45RBlo, demonstrating that CD45RB status acts as an affinity-based differentiation switch on CD8+ T cells. Thus, these data establish a novel mechanism by which CD45 isoforms tune low affinity primed memory CD8+ T to become potent secondary effectors following heterologous rechallenge. These findings have direct implications for allogeneic heterologous immunity by demonstrating that despite a lower precursor frequency, low affinity priming is sufficient to generate memory cells that mediate potent secondary responses against a cross-reactive graft challenge.

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Advances in Direct T-Cell Alloreactivity: Function, Avidity, Biophysics and Structure

Cited by 27 publications

References 132 publications

Benefits of Using CD45RA and CD28 to Investigate CD8 Subsets in Kidney Transplant Recipients

Benefits of Using CD45RA and CD28 to Investigate CD8 Subsets in Kidney Transplant Recipients

Effector Mechanisms of Rejection

Low-Affinity Memory CD8+ T Cells Mediate Robust Heterologous Immunity

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