A Significant Expansion of CD8+ CD28− T-Suppressor Cells in Adult-to-Adult Living Donor Liver Transplant Recipients

Lin, Yunfeng; Yan, Lü-Nan; Li, B.; Wang, L.-L.; Wen, Tianfu; Zeng, Yong; Wang, W.-T.; Zhao, Jingyi; Yang, Jiqiao; Xu, Meiqing; Ma, Yuanji; Chen, Z.-Y.; Bai, Yang

doi:10.1016/j.transproceed.2009.09.072

Cited by 33 publications

(30 citation statements)

References 11 publications

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“…12,31-33 These cells have been demonstrated to play a strong immunosuppressive role in the context of allograft rejection. A distinct population of antigen specific CD8 + CD28 − T cells can be generated in vitro by repeatedly stimulating human peripheral blood mononuclear cells with allogeneic or xenogeneic APCs.…”

Section: Transplantation and Cd28− T Cellsmentioning

confidence: 99%

“…Elevated Ts levels in adult liver transplant patients have been associated with better graft function and reduced rejection rates. 31 Additionally, non-rejecting transplant patients were observed to have Ts that induced ILT3 expression and reduced CD80/86 expression on APCs whereas rejecting transplant patients had lower amounts of Ts in circulation that did not induce this tolerogenic APC profile. 36-39 These findings suggest that there exists a CD8 + CD28 − T suppressor subset that confers immunosuppression and thus promotes allograft tolerance.…”

Section: Transplantation and Cd28− T Cellsmentioning

confidence: 99%

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CD28 Negative T Cells: Is Their Loss Our Gain?

Mou

Espinosa

et al. 2014

American Journal of Transplantation

109

104

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CD28 is a primary costimulation molecule for T cell activation. However, during the course of activation some T cells lose this molecule and assume a CD28-independent existence. These CD28− T cells are generally antigen-experienced and highly differentiated. CD28− T cells are functionally heterogeneous. Their characteristics vary largely on the context in which they are found and range from having enhanced cytotoxic abilities to promoting immune regulation. Thus, CD28 loss appears to be more of a marker for advanced differentiation regardless of the cytotoxic or regulatory function being conducted by the T cell. CD28− T cells are now being recognized as playing significant roles in several human diseases. Various functional CD28− populations have been characterized in inflammatory conditions, infections, and cancers. Of note, the recent introduction of costimulation blockade-based therapies, particularly those that inhibit CD28-B7 interactions, has made CD28 loss particularly relevant for solid organ transplantation. Certain CD28− T cell populations seem to promote allograft tolerance whereas others contribute to alloreactivity and costimulation blockade resistant rejection. Elucidating the interplay between these populations and characterizing the determinants of their ultimate function may have relevance for clinical risk stratification and personal determination of optimal post-transplant immune management.

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Section: Transplantation and Cd28− T Cellsmentioning

confidence: 99%

Section: Transplantation and Cd28− T Cellsmentioning

confidence: 99%

CD28 Negative T Cells: Is Their Loss Our Gain?

Mou

Espinosa

et al. 2014

American Journal of Transplantation

109

104

View full text Add to dashboard Cite

show abstract

“…− T cells are found predominantly within the (terminally differentiated) effector memory CD8 + T cell subset [40] and they can have cytotoxic [29,[41][42][43] or immunosuppressive functions [10,[44][45][46][47]. Thus, inhibition of CD8…”

Section: Cd28mentioning

confidence: 99%

Mesenchymal stem cells control alloreactive CD8+CD28− T cells

Engela

Baan

Litjens

et al. 2013

Clinical and Experimental Immunology

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“…The appearance of regulatory CD8 + CD28 2 T suppressor cells is associated with a reduced need for maintenance of immunosuppression in pediatric liver-intestine transplant recipients (Sindhi et al, 2005), as well as in adult-to-adult living donor liver transplantation (Lin et al, 2009). Studies in heart transplant patients indicate that CD8 + CD28 2 T suppressor cells upregulate the inhibitory receptors ILT-3 and ILT-4 on APCs (Chang et al, 2002).…”

Section: Physiological Relevance Of the Inhibitory Effect Of Hmscs Onmentioning

confidence: 99%

Human mesenchymal stem cells shift CD8+ T cells towards a suppressive phenotype by inducing tolerogenic monocytes

Hof-Nahor¹,

Leshansky²,

Shivtiel³

et al. 2012

Journal of Cell Science

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SummaryThe mechanisms underlying the immunomodulatory effects of mesenchymal stem cells (MSCs) have been investigated under extreme conditions of strong T cell activation, which induces the rapid death of activated lymphocytes. The objective of this study was to investigate these mechanisms in the absence of additional polyclonal activation. In co-cultures of peripheral mononuclear blood cells with human MSCs (hereafter referred to as hMSCs), we observed a striking decrease in the level of CD8 expression on CD8+ cells, together with decreased expression of CD28 and CD44, and impaired production of IFN-gamma and Granzyme B. This effect was specific to hMSCs, because it was not observed with several other cell lines. Downregulation of CD8 expression required CD14+ monocytes to be in direct contact with the CD8+ cells, whereas the effects of hMSCs on the CD14+ cells were essentially mediated by soluble factors. The CD14+ monocytes exhibited a tolerogenic pattern when co-cultured with hMSCs, with a clear decrease in CD80 and CD86 co-stimulatory molecules, and an increase in the inhibitory receptors ILT-3 and ILT-4. CD8+ cells that were preconditioned by MSCs had similar effects on monocytes and were able to inhibit lymphocyte proliferation. Injection of hMSCs in humanized NSG mice showed similar trends, in particular decreased levels of CD44 and CD28 in human immune cells. Our study demonstrates a new immunomodulation mechanism of action of hMSCs through the modulation of CD8+ cells towards a non-cytotoxic and/or suppressive phenotype. This mechanism of action has to be taken into account in clinical trials, where it should be beneficial in grafts and autoimmune diseases, but potentially detrimental in malignant diseases.

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A Significant Expansion of CD8+ CD28− T-Suppressor Cells in Adult-to-Adult Living Donor Liver Transplant Recipients

Cited by 33 publications

References 11 publications

CD28 Negative T Cells: Is Their Loss Our Gain?

CD28 Negative T Cells: Is Their Loss Our Gain?

Mesenchymal stem cells control alloreactive CD8+CD28− T cells

Human mesenchymal stem cells shift CD8+ T cells towards a suppressive phenotype by inducing tolerogenic monocytes

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