CD28−CD8+ T cells do not contain unique clonotypes and are therefore dispensable

Weinberger, Birgit; Welzl, Kathrin; Herndler‐Brandstetter, Dietmar; Parson, Walther; Grubeck‐Loebenstein, Beatrix

doi:10.1016/j.imlet.2009.08.008

Cited by 21 publications

(28 citation statements)

References 63 publications

(85 reference statements)

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“…To analyze the clonal composition of BM derived T cells of a certain specificity, we stimulated BMMC as well as PBMC with the peptide CMV NLV for two weeks following a previously published protocol [9,10]. It was of interest that the starting population from the BM contained more CMV NLV specific cells than the corresponding population from the PB (12.5% ± 3.2, n = 5: BM versus 5.0% ± 3.6; n = 5: PB; p < 0.01).…”

Section: Resultsmentioning

confidence: 99%

“…During this time they were restimulated with IL-2 (20 ng/ml) (Novartis) every three days and with peptide once on day 7. After 14 days CMV NLV specific CD8 + T cells were purified using MACS technology, as previously described [10]. Briefly, CMV specific CD8 + T cells were positively selected using APC-coupled CMV NLV pentamers, followed by the addition of anti-APC-antibodies coupled with magnetic beads (all (BD Pharmingen) and a LS column (Miltenyi Biotec).…”

Section: Methodsmentioning

confidence: 99%

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Bone marrow T cells from the femur are similar to iliac crest derived cells in old age and represent a useful tool for studying the aged immune system

Pritz

Landgraf-Rauf

Herndler‐Brandstetter

et al. 2013

Immun Ageing

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BackgroundCD4+ and CD8+ T cells reside in the human bone marrow (BM) and show a heightened activation state. However, only small sample sizes are available from sources such as the iliac crest. Larger samples can be obtained from the femur in the course of hip replacement surgery. It was therefore the goal of the present study to compare the phenotype and function of BM T cells from different sources from elderly persons and to investigate how femur derived bone marrow T cells can serve as a tool to gain a better understanding of the role of adaptive immune cells in the BM in old age.ResultsBone marrow mononuclear cells (BMMC) were isolated from either the iliac crest or the femur shaft. As expected the yield of mononuclear cells was higher from femur than from iliac crest samples. There were no phenotypic differences between BMMC from the two sources. Compared to PBMC, both BM sample types contained fewer naïve and more antigen experienced CD4+ as well as CD8+ T cells, which, in contrast to peripheral cells, expressed CD69. Cytokine production was also similar in T cells from both BM types. Larger sample sizes allowed the generation of T cell lines from femur derived bone marrow using non-specific as well as specific stimulation. The phenotype of T cell lines generated by stimulation with OKT-3 and IL-2 for two weeks was very similar to the one of ex vivo BM derived T cells. Such lines can be used for studies on the interaction of different types of BM cells as shown by co-culture experiments with BM derived stromal cells. Using CMVNLV specific T cell lines we additionally demonstrated that BM samples from the femur are suitable for the generation of antigen specific T cell lines, which can be used in studies on the clonal composition of antigen specific BM T cells.ConclusionIn conclusion, our results demonstrate that BMMC from the femur shaft are a useful tool for studies on the role of T cells in the BM in old age.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Bone marrow T cells from the femur are similar to iliac crest derived cells in old age and represent a useful tool for studying the aged immune system

Pritz

Landgraf-Rauf

Herndler‐Brandstetter

et al. 2013

Immun Ageing

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“…49-51 Finally, there exists the possibility that CD28 − T cells may just be residual cells from prior antigen exposures that do not offer any unique clonotypes, and thus are largely dispensable. 14 In any event, achieving a higher resolution of understanding in this interplay of costimulation and coinhibitory pathways in the context of CD28 loss will play an immense role in therapeutic development for many human diseases.…”

Section: Discussionmentioning

confidence: 99%

“…14 This consequently leads to an immune system compromised by limited antigenic diversity. Furthermore, age-related thymic involution and its related reduced output in naïve CD28+ T cells may also contribute to an aged and weakened immune phenotype.…”

Section: Clinical Relevance Of Cd28− T Cellsmentioning

confidence: 99%

CD28 Negative T Cells: Is Their Loss Our Gain?

Mou

Espinosa

et al. 2014

American Journal of Transplantation

110

108

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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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“…Recent studies have shown that the same clonotypes occur in both, early memory CD8 + T cells and highly differentiated CD8 + CD28 -T cells, indicating no loss of unique T cell specificities when depleting CD8 + CD28 -T cells [137,138]. For example, the depletion of autoreactive immunologic memory followed by autologous hematopoietic stem cell transplantation in patients with refractory systemic lupus erythematosus induced long-term remission through de novo generation of a juvenile and tolerant immune system [139].…”

Section: Strategiesmentioning

confidence: 99%

The Aging of the Adaptive Immune System

Herndler‐Brandstetter¹,

Weinberger²,

Pfister³

et al. 2011

CIR

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Adaptive immune responses are severely affected by the aging process as reflected by an increased morbidity and mortality from infectious diseases and a low efficacy of vaccination in elderly persons. Age-related changes within the bone marrow and thymus lead to an impaired generation of new T and B cells severely compromising the maintenance of a diverse and balanced T and B cell repertoire in old age. The maintenance of a balanced T cell repertoire is further challenged by latent persistent infections, such as Cytomegalovirus. Understanding the mechanisms of age-related alterations of the adaptive immune response may help to facilitate the development of more efficient vaccines for elderly persons and to envisage strategies to overcome immunosenescence.

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CD28−CD8+ T cells do not contain unique clonotypes and are therefore dispensable

Cited by 21 publications

References 63 publications

Bone marrow T cells from the femur are similar to iliac crest derived cells in old age and represent a useful tool for studying the aged immune system

Bone marrow T cells from the femur are similar to iliac crest derived cells in old age and represent a useful tool for studying the aged immune system

CD28 Negative T Cells: Is Their Loss Our Gain?

The Aging of the Adaptive Immune System

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