TCR spectratyping revealed T lymphocytes associated with graft-versus-host disease after allogeneic hematopoietic stem cell transplantation

Du, Jiang; Gu, Jiangying; Liu, Jing; Cen, Xiaowei; Zhang, Ying; Ou, Yuan; Chu, Bin; Zhu, Ping

doi:10.1080/10428190701474357

Cited by 19 publications

(21 citation statements)

References 28 publications

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“…153 Similar results were seen in prior studies using CDR3 spectratyping. 155,156 In contrast, another study utilizing deep sequencing methods reported that grade 2-3 acute GVHD is actually associated with a higher TCR diversity than those who developed grade 0-1 acute GVHD, suggesting that GVHD did not restrict recovery of TCR repertoire. 154 The differences noted in these studies are a reflection of different graft and donor sources, conditioning regimens and the use of T cell depletion.…”

Section: Assessment Of T Cell Receptor Repertoirementioning

confidence: 86%

Immune reconstitution post allogeneic transplant and the impact of immune recovery on the risk of infection

2016

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Infection is the leading cause of non-relapse mortality after allogeneic haematopoietic cell transplantation (HCT). This occurs as a result of dysfunction to the host immune system from the preparative regimen used prior to HCT, combined with a delay in reconstitution of the donorderived immune system after HCT. In this article, we elaborate on the process of immune reconstitution post-HCT that begins with the innate system and is followed by recovery of adaptive immunity. Simultaneously, we describe how the tempo of immune reconstitution influences the risk of various infections. We explain some of the key differences in immune reconstitution and the consequent risk of infections in recipients of peripheral blood stem cell, bone marrow or umbilical cord blood grafts. Other factors that impact on immune recovery are also highlighted. Finally, we allude to various strategies that are being tested to enhance immune reconstitution post-HCT.

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Section: Assessment Of T Cell Receptor Repertoirementioning

confidence: 86%

Immune reconstitution post allogeneic transplant and the impact of immune recovery on the risk of infection

2016

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“…Further, the dominant Vβ expansions differed amongst littermates although human PBMCs from a single donor was used for transplantation in for each experiment, which also suggests that the selection of particular Vβ was a stochastic effect and does not represent a selective outgrowth of immunodominant clones. Distinct oligoclonal T cell expansions have also been reported in human GVHD after stem cell transplantation [21, 22, 23, 24]. Whether IL-10 has a modulatory role with IL-2 in shaping the T cell repertoire in the GVHD response is not known but it is possible that increased bioavalibility of the two cytokines could influence TCR repertoire at sites of GVHD activity.…”

Section: Discussionmentioning

confidence: 99%

Combination of IL-10 and IL-2 induces oligoclonal human CD4 T cell expansion during xenogeneic and allogeneic GVHD in humanized mice

Abraham

Guo

Choi

et al. 2017

Heliyon

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IL-10 is a crucial anti-inflammatory cytokine which can also exert a seemingly divergent immunostimulatory effects under certain conditions. We found high levels of the cytokine in a xenogeneic GVHD model where NOD-scid IL2rγcnull (NSG) mice were transplanted with human PBMCs in presence of IL-2. Presence of exogenous IL-10 altered the kinetics of IL-2 induced human T cell reconstitution in vivo, showing an initial delay, followed by rapid expansion. Further, compared to IL-2 alone, treatment with IL-2 in combination with IL-10 increased survival in most animals and completely protected ∼20% of mice from GVHD. Additionally, IL-2 induced expansion of both CD4+ and CD8+ xenoreactive T cells whereas a combination of IL-2 and IL-10 resulted in selective expansion of CD4+ T cells only. TCR Vβ repertoire analysis of CD4+ T cells showed that in contrast to IL-2 alone, simultaneous presence of both cytokines drastically reduced the Vβ repertoire of the expanded CD4+ T cells. Highly restricted Vβ usage was also observed when the cytokine combination was tested in an allogeneic GVHD model where NOD-scid IL2rγcnull mice expressing HLA-DR4 (NSG-DR4) were transplanted with purified CD4+ T cells from HLA-DR4 negative donors. Taken together, our results demonstrate that IL-10 can profoundly modulate the subset composition and repertoire of responding T cells during GVHD.

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“…Molecular structural analysis has revealed that CDR3 mainly recognizes MHC molecules bound to antigenic peptides [20, 21]. Hence, analysis of CDR3 can reveal changes in antigen-stimulated T cells [22, 23], the number of T cell clones, and T cell functioning [24, 25]. …”

Section: Discussionmentioning

confidence: 99%

High-Throughput Analysis of the T Cell Receptor Beta Chain Repertoire in PBMCs from Chronic Hepatitis B Patients with HBeAg Seroconversion

Huang

Liu

et al. 2016

Canadian Journal of Infectious Diseases and Medical Microbiolog

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T lymphocytes are the most important immune cells that affect both the development and treatment of hepatitis B. We used high-throughput sequencing to determine the diversity in the V and J regions of the TCRβ chain in 4 chronic hepatitis B patients before and after HBeAg seroconversion. Here, we demonstrate that the 4 patients expressed Vβ12-4 at the highest frequencies of 10.6%, 9.2%, 17.5%, and 7.5%, and Vβ28 was the second most common, with frequencies of 7.8%, 6.7%, 5.3%, and 10.9%, respectively. No significant changes were observed following seroconversion. With regard to the Jβ gene, Jβ2-1 was the most commonly expressed in the 4 patients at frequencies of 5.8%, 6.5%, 11.3%, and 7.3%, respectively. Analysis of the V-J region genes revealed several differences, including significant increases in the expression levels of V7-2-01-J2-1, V12-4-J1-1, and V28-1-J1-5 and a decrease in that of V19-01-J2-3. These results illustrate the presence of biased TCRVβ and Jβ gene expression in the chronic hepatitis B patients. TRBVβ12-4, Vβ28, Jβ2-1, V7-2-01-J2-1, V12-4-J1-1, and V28-1-J1-5 may be associated with the development and treatment of CHB.

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TCR spectratyping revealed T lymphocytes associated with graft-versus-host disease after allogeneic hematopoietic stem cell transplantation

Cited by 19 publications

References 28 publications

Immune reconstitution post allogeneic transplant and the impact of immune recovery on the risk of infection

Immune reconstitution post allogeneic transplant and the impact of immune recovery on the risk of infection

Combination of IL-10 and IL-2 induces oligoclonal human CD4 T cell expansion during xenogeneic and allogeneic GVHD in humanized mice

High-Throughput Analysis of the T Cell Receptor Beta Chain Repertoire in PBMCs from Chronic Hepatitis B Patients with HBeAg Seroconversion

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