Ex vivo expansion of human CD4+CD25high regulatory T cells from transplant recipients permits functional analysis of small blood samples

Kreijveld, Ellen; Koenen, Hans J. P. M.; Hilbrands, Luuk B.; Joosten, Irma

doi:10.1016/j.jim.2006.06.001

Cited by 17 publications

(17 citation statements)

References 25 publications

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“…For 3 rd party controls, buffy coats were obtained from healthy blood donors (Sanquin Blood Bank region South East, Nijmegen, the Netherlands). Cell isolation and culture were conducted as described elsewhere [21]. All cells from donors and recipients were frozen prior to use in analyses.…”

Section: Methodsmentioning

confidence: 99%

Immunological Monitoring of Renal Transplant Recipients to Predict Acute Allograft Rejection Following the Discontinuation of Tacrolimus

et al. 2008

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BackgroundTransplant patients would benefit from reduction of immunosuppression providing that graft rejection is prevented. We have evaluated a number of immunological markers in blood of patients in whom tacrolimus was withdrawn after renal transplantation. The alloreactive precursor frequency of CD4+ and CD8+ T cells, the frequency of T cell subsets and the functional capacity of CD4+CD25+FoxP3+ regulatory T cells (Treg) were analyzed before transplantation and before tacrolimus reduction. In a case-control design, the results were compared between patients with (n = 15) and without (n = 28) acute rejection after tacrolimus withdrawal.Principal FindingsPrior to tacrolimus reduction, the ratio between memory CD8+ T cells and Treg was higher in rejectors compared to non-rejectors. Rejectors also had a higher ratio between memory CD4+ T cells and Treg, and ratios <20 were only observed in non-rejectors. Between the time of transplantation and the start of tacrolimus withdrawal, an increase in naive T cell frequencies and a reciprocal decrease of effector T cell percentages was observed in rejectors. The proportion of Treg within the CD4+ T cells decreased after transplantation, but anti-donor regulatory capacity of Treg remained unaltered in rejectors and non-rejectors.ConclusionsImmunological monitoring revealed an association between acute rejection following the withdrawal of tacrolimus and 1) the ratio of memory T cells and Treg prior to the start of tacrolimus reduction, and 2) changes in the distribution of naive, effector and memory T cells over time. Combination of these two biomarkers allowed highly specific identification of patients in whom immunosuppression could be safely reduced.

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Section: Methodsmentioning

confidence: 99%

Immunological Monitoring of Renal Transplant Recipients to Predict Acute Allograft Rejection Following the Discontinuation of Tacrolimus

et al. 2008

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“…Other groups have successfully used similar methods to expand polyclonal Tregs from healthy donors 18 , diabetic patients 19 , transplant recipients 20 or antigen-specific Tregs from HCV patients 21 but, to our knowledge, this is the first description of a successful protocol to expand functional Tregs from HIV-1 positive donors.…”

Section: Discussionmentioning

confidence: 99%

New Tools to Expand Regulatory T Cells from HIV-1-infected Individuals

Angin

King

Addo

2013

JoVE

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CD4+ Regulatory T cells (Tregs) are potent immune modulators and serve an important function in human immune homeostasis. Depletion of Tregs has led to measurable increases in antigen-specific T cell responses in vaccine settings for cancer and infectious pathogens. However, their role in HIV-1 immuno-pathogenesis remains controversial, as they could either serve to suppress deleterious HIV-1-associated immune activation and thus slow HIV-1 disease progression or alternatively suppress HIV-1-specific immunity and thereby promote virus spread. Understanding and modulating Treg function in the context of HIV-1 could lead to potential new strategies for immunotherapy or HIV vaccines. However, important open questions remain on their role in the context of HIV-1 infection, which needs to be carefully studied. Representing roughly 5% of human CD4+ T cells in the peripheral blood, studying the Treg population has proven to be difficult, especially in HIV-1 infected individuals where HIV-1-associated CD4 T cell and with that Treg depletion occurs. The characterization of regulatory T cells in individuals with advanced HIV-1 disease or tissue samples, for which only very small biological samples can be obtained, is therefore extremely challenging. We propose a technical solution to overcome these limitations using isolation and expansion of Tregs from HIV-1-positive individuals. Here we describe an easy and robust method to successfully expand Tregs isolated from HIV-1-infected individuals in vitro. Flow-sorted CD3+CD4+CD25+CD127low Tregs were stimulated with anti-CD3/anti-CD28 coated beads and cultured in the presence of IL-2. The expanded Tregs expressed high levels of FOXP3, CTLA4 and HELIOS compared to conventional T cells and were shown to be highly suppressive. Easier access to large numbers of Tregs will allow researchers to address important questions concerning their role in HIV-1 immunopathogenesis. We believe answering these questions may provide useful insight for the development of an effective HIV-1 vaccine.

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“…Efforts are currently devoted to the identification of markers of graft acceptance likely to contribute to minimize immunosuppression. The role of the mTreg/Treg balance in the dynamics of treatment is one of the main issues requiring elucidation (125). …”

Section: Regulatory T Cellmentioning

confidence: 99%

Regulatory T Cell and Forkhead Box Protein 3 as Modulators of Immune Homeostasis

et al. 2017

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The transcription factor forkhead box protein 3 (FOXP3) is an essential molecular marker of regulatory T cell (Treg) development in different microenvironments. Tregs are cells specialized in the suppression of inadequate immune responses and the maintenance of homeostatic tolerance. Studies have addressed and elucidated the role played by FOXP3 and Treg in countless autoimmune and infectious diseases as well as in more specific cases, such as cancer. Within this context, the present article reviews aspects of the immunoregulatory profile of FOXP3 and Treg in the management of immune homeostasis, including issues relating to pathology as well as immune tolerance.

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Ex vivo expansion of human CD4+CD25high regulatory T cells from transplant recipients permits functional analysis of small blood samples

Cited by 17 publications

References 25 publications

Immunological Monitoring of Renal Transplant Recipients to Predict Acute Allograft Rejection Following the Discontinuation of Tacrolimus

Immunological Monitoring of Renal Transplant Recipients to Predict Acute Allograft Rejection Following the Discontinuation of Tacrolimus

New Tools to Expand Regulatory T Cells from HIV-1-infected Individuals

Regulatory T Cell and Forkhead Box Protein 3 as Modulators of Immune Homeostasis

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