Cytomegalovirus‐Specific Regulatory and Effector T Cells Share TCR Clonality—Possible Relation to Repetitive CMV Infections

Cytomegalovirus (CMV) infections have a major impact on morbidity and mortality of transplant patients. Among the complex antiviral T‐cell response, CMV‐IE‐1 antigen‐specific CD8+ cells are crucial for preventing CMV disease but do not protect from recurring/lasting CMV reactivation. Recently, we confirmed that adoptive transfer of autologous IE‐1/pp65‐specific T‐cell lines was able to combat severe CMV disease; however, the control of CMV infection was only temporary. We hypothesized that CMV‐induced regulatory T cells (iTreg) might be related to recurring/lasting CMV infection.

[1]  A. Olek,et al.  A modified and improved method for bisulphite based cytosine methylation analysis. , 1996, Nucleic acids research.

[2]  J. Schneider-Mergener,et al.  T-cell epitope mapping by flow cytometry , 1998, Nature Medicine.

[3]  F. Kern,et al.  Mechanisms of human cytomegalovirus (HCMV) (re)activation and its impact on organ transplant patients , 1999, Transplant infectious disease : an official journal of the Transplantation Society.

[4]  D. Mason,et al.  Peripheral Autoantigen Induces Regulatory T Cells that Prevent Autoimmunity , 1999, The Journal of experimental medicine.

[5]  H. Volk,et al.  Analysis of CD8 T cell reactivity to cytomegalovirus using protein‐spanning pools of overlapping pentadecapeptides , 2000, European journal of immunology.

[6]  Ethan M. Shevach,et al.  CD4+CD25+ suppressor T cells: more questions than answers , 2002, Nature Reviews Immunology.

[7]  J. Michálek,et al.  Selective depletion of donor alloreactive T cells without loss of antiviral or antileukemic responses. , 2003, Blood.

[8]  B. Rouse,et al.  CD4+CD25+ T Cells Regulate Virus-specific Primary and Memory CD8+ T Cell Responses , 2003, The Journal of experimental medicine.

[9]  M Hummel,et al.  Design and standardization of PCR primers and protocols for detection of clonal immunoglobulin and T-cell receptor gene recombinations in suspect lymphoproliferations: Report of the BIOMED-2 Concerted Action BMH4-CT98-3936 , 2003, Leukemia.

[10]  H. von Boehmer,et al.  In Vivo Instruction of Suppressor Commitment in Naive T Cells , 2004, The Journal of experimental medicine.

[11]  C. Baecher-Allan,et al.  Human CD4+CD25+ regulatory T cells. , 2004, Seminars in immunology.

[12]  R. V. van Lier,et al.  Properties of CD4(+) T cells in human cytomegalovirus infection. , 2004, Human immunology.

[13]  M. Suthanthiran,et al.  ENHANCED GRANULYSIN mRNA EXPRESSION IN URINARY SEDIMENT IN EARLY AND DELAYED ACUTE RENAL ALLOGRAFT REJECTION , 2004, Transplantation.

[14]  Shimon Sakaguchi,et al.  Foxp3: a critical regulator of the development and function of regulatory T cells. , 2004, Microbes and infection.

[15]  C. O'keefe,et al.  Pathologic clonal cytotoxic T-cell responses: nonrandom nature of the T-cell-receptor restriction in large granular lymphocyte leukemia. , 2005, Blood.

[16]  J. Lohr,et al.  Sequential development of interleukin 2–dependent effector and regulatory T cells in response to endogenous systemic antigen , 2005, The Journal of experimental medicine.

[17]  C. Rooney,et al.  HLA type‐independent generation of antigen‐specific T cells for adoptive immunotherapy , 2005, European journal of immunology.

[18]  A. Rudensky,et al.  Regulatory T cell lineage specification by the forkhead transcription factor foxp3. , 2005, Immunity.

[19]  Louis J. Picker,et al.  Broadly targeted human cytomegalovirus-specific CD4+ and CD8+ T cells dominate the memory compartments of exposed subjects , 2005, The Journal of experimental medicine.

[20]  M. Roncarolo,et al.  Phenotypic and functional differences between human CD4+CD25+ and type 1 regulatory T cells. , 2005, Current topics in microbiology and immunology.

[21]  R. Hetzer,et al.  Protection from cytomegalovirus after transplantation is correlated with immediate early 1–specific CD8 T cells , 2005, The Journal of experimental medicine.

[22]  S. Sakaguchi.  Naturally arising Foxp3-expressing CD25+CD4+ regulatory T cells in immunological tolerance to self and non-self , 2005, Nature Immunology.

[23]  M. Nussenzweig,et al.  Inducing and expanding regulatory T cell populations by foreign antigen , 2005, Nature Immunology.

[24]  Yasmine Belkaid,et al.  Natural regulatory T cells in infectious disease , 2005, Nature Immunology.

[25]  L. Gondek,et al.  Molecular strategies for detection and quantitation of clonal cytotoxic T-cell responses in aplastic anemia and myelodysplastic syndrome. , 2006, Blood.

[26]  A. Akbar,et al.  Human CD4+ CD25hi Foxp3+ regulatory T cells are derived by rapid turnover of memory populations in vivo. , 2006, The Journal of clinical investigation.

[27]  J. Lohr,et al.  Regulatory T cells in the periphery , 2006, Immunological reviews.

[28]  F. Powrie,et al.  Emerging Challenges in Regulatory T Cell Function and Biology , 2007, Science.

[29]  R. Steinman,et al.  Dendritic cell–expanded, islet-specific CD4+ CD25+ CD62L+ regulatory T cells restore normoglycemia in diabetic NOD mice , 2007, The Journal of experimental medicine.

[30]  Edgar Schmitt,et al.  Epigenetic Control of the foxp3 Locus in Regulatory T Cells , 2007, PLoS biology.

[31]  I. Türbachova,et al.  DNA demethylation in the human FOXP3 locus discriminates regulatory T cells from activated FOXP3+ conventional T cells , 2007, European journal of immunology.

[32]  A. Sant,et al.  CD4+CD25+ Regulatory T Cell Repertoire Formation Shaped by Differential Presentation of Peptides from a Self-Antigen1 , 2008, The Journal of Immunology.

[33]  M. Roncarolo,et al.  Is FOXP3 a bona fide marker for human regulatory T cells? , 2008, European journal of immunology.

[34]  Yaling Zhou.  Regulatory T cells and viral infections. , 2008, Frontiers in bioscience : a journal and virtual library.

[35]  R. Freeman.  The 'indirect' effects of cytomegalovirus infection. , 2009, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[36]  S. Sakaguchi,et al.  Regulatory T cells: how do they suppress immune responses? , 2009, International immunology.

[37]  H. Volk,et al.  Adoptive T‐Cell Therapy of a Lung Transplanted Patient with Severe CMV Disease and Resistance to Antiviral Therapy , 2009, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[38]  H. Volk,et al.  Generation of HCMV-specific T-cell Lines From Seropositive Solid-organ-transplant Recipients for Adoptive T-cell Therapy , 2009, Journal of immunotherapy.

[39]  Alf Hamann,et al.  Epigenetic control of FOXP3 expression: the key to a stable regulatory T-cell lineage? , 2009, Nature Reviews Immunology.

[40]  F. Kern,et al.  High levels of CMV-IE-1-specific memory T cells are associated with less alloimmunity and improved renal allograft function. , 2009, Transplant immunology.

[41]  Y. Belkaid,et al.  Expression of Helios, an Ikaros Transcription Factor Family Member, Differentiates Thymic-Derived from Peripherally Induced Foxp3+ T Regulatory Cells , 2010, The Journal of Immunology.

[42]  T. Reischig.  Cytomegalovirus-associated renal allograft rejection: new challenges for antiviral preventive strategies , 2010, Expert review of anti-infective therapy.

[43]  J. C. Castón Osorio,et al.  [Indirect effects of cytomegalovirus infection]. , 2011, Enfermedades infecciosas y microbiologia clinica.

[44]  A. Liston,et al.  Regulatory T Cells , 2011, Methods in Molecular Biology.