Immunosuppressive Drugs and Tregs

Serres, Sacha A. De; Sayegh, Mohamed H.; Najafian, Nader

doi:10.2215/cjn.03180509

Cited by 63 publications

(41 citation statements)

References 87 publications

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“…Although caution must be exercised before attributing tolerogenic properties to alemtuzumab in the pediatric setting, our data suggest that alemtuzumab does not have the initial detrimental effect on Treg frequency seen with other induction agents. 21,22 The slow decrease in the Tregs/T EM ratio observed after 12 months is consonant with the hypothesis that the ratio of Tregs/memory T cells might decrease after homeostatic repopulation of the T cell compartment. 23 All in all, it is tempting to speculate that the use of alemtuzumab in children might hamper the rapid homeostatic proliferation of memory T cells seen initially after depletion, potentially favoring long-term hyporesponsiveness to the graft.…”

Section: Discussionsupporting

confidence: 68%

Immune Profile of Pediatric Renal Transplant Recipients following Alemtuzumab Induction

Serres

Mfarrej

Magee

et al. 2012

Journal of the American Society of Nephrology

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The incidence of developing circulating anti-human leukocyte antigen antibodies and the kinetics of T cell depletion and recovery among pediatric renal transplant recipients who receive alemtuzumab induction therapy are unknown. In a collaborative endeavor to minimize maintenance immunosuppression in pediatric renal transplant recipients, we enrolled 35 participants from four centers and treated them with alemtuzumab induction therapy and a steroid-free, calcineurin-inhibitor-withdrawal maintenance regimen. At 3 months after transplant, there was greater depletion of CD4 + than CD8 + T cells within the total, naive, memory, and effector memory subsets, although depletion of the central memory subset was similar for CD4 + and CD8 + cells. Although CD8 + T cells recovered faster than CD4 + subsets overall, they failed to return to pretransplant levels by 24 months after transplant. There was no evidence for greater recovery of either CD4 + or CD8 + memory cells than naïve cells. Alemtuzumab relatively spared CD4 + CD25 + FoxP3 + regulatory T cells, resulting in a rise in their numbers relative to total CD4 + cells and a ratio that remained at least at pretransplant levels throughout the study period. Seven participants (20%) developed anti-human leukocyte antigen antibodies without adversely affecting allograft function or histology on 2-year biopsies. Long-term follow-up is underway to assess the potential benefits of this regimen in children.

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Section: Discussionsupporting

confidence: 68%

Immune Profile of Pediatric Renal Transplant Recipients following Alemtuzumab Induction

Serres

Mfarrej

Magee

et al. 2012

Journal of the American Society of Nephrology

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“…For example, some groups found that CSA reduced the function and level of Treg cells (87)(88)(89), but other evidence showed that CSA could induce Treg cells (76,77,90,91). This discrepancy may be due to dose effects because we observed that a lower dose CSA was more effective in inducing Treg cells than was a higher dose (Fig.…”

Section: Discussionmentioning

confidence: 61%

“…CSA binds to the cytosolic protein cyclophilin and inhibits calcineurin of T cells, consequently suppressing transcription of IL-2 (69)(70)(71)(72)(73). It also interferes with DC to T cell interaction (74) and can be used to induce Treg cells (75)(76)(77). Moreover, the concept of immunizing with Ag together with an immunosuppressant to induce Treg cells and effectively treat autoimmune diseases has previously been proven in animal models (78,79).…”

mentioning

confidence: 99%

A Recombinant G Protein Plus Cyclosporine A–Based Respiratory Syncytial Virus Vaccine Elicits Humoral and Regulatory T Cell Responses against Infection without Vaccine-Enhanced Disease

Zhou

Zhong

et al. 2016

The Journal of Immunology

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Respiratory syncytial virus (RSV) infection can cause severe disease in the lower respiratory tract of infants and older people. Vaccination with a formalin-inactivated RSV vaccine (FI-RSV) and subsequent RSV infection has led to mild to severe pneumonia with two deaths among vaccinees. The vaccine-enhanced disease (VED) was recently demonstrated to be due to an elevated level of Th2 cell responses following loss of regulatory T (Treg) cells from the lungs. To induce high levels of neutralizing Abs and minimize pathogenic T cell responses, we developed a novel strategy of immunizing animals with a recombinant RSV G protein together with cyclosporine A. This novel vaccine induced not only a higher level of neutralizing Abs against RSV infection, but, most importantly, also significantly higher levels of Treg cells that suppressed VED in the lung after RSV infection. The induced responses provided protection against RSV challenge with no sign of pneumonia or bronchitis. Treg cell production of IL-10 was one of the key factors to suppress VED. These finding indicate that G protein plus cyclosporine A could be a promising vaccine against RSV infection in children and older people.

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“…In our model, given that Tregs were rarely detected in the peripheral blood or allograft in control-treated mice, the principal effect of FR104 is likely to be the suppression of effector T cell activity and the skewing of the effector/Treg balance. As a combination therapy, FR104 with Treg cellular therapy is a promising strategy for future clinical use, particularly with the majority of other immunosuppressants displaying a propensity to reduce Treg activity and survival (40). In conclusion, the selective blockade of CD28 costimulation during the activation of T cells reduces the inflammatory graft infiltrate and alone prolongs human skin allograft survival.…”

Section: Discussionmentioning

confidence: 99%

Selective blockade of CD28 on human T cells facilitates regulation of alloimmune responses

et al. 2017

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Immunosuppressive Drugs and Tregs

Cited by 63 publications

References 87 publications

Immune Profile of Pediatric Renal Transplant Recipients following Alemtuzumab Induction

Immune Profile of Pediatric Renal Transplant Recipients following Alemtuzumab Induction

A Recombinant G Protein Plus Cyclosporine A–Based Respiratory Syncytial Virus Vaccine Elicits Humoral and Regulatory T Cell Responses against Infection without Vaccine-Enhanced Disease

Selective blockade of CD28 on human T cells facilitates regulation of alloimmune responses

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