Dataset Information

Tissue reservoirs of antiviral T cell immunity in persistent human CMV infection.

ABSTRACT: T cell responses to viruses are initiated and maintained in tissue sites; however, knowledge of human antiviral T cells is largely derived from blood. Cytomegalovirus (CMV) persists in most humans, requires T cell immunity to control, yet tissue immune responses remain undefined. Here, we investigated human CMV-specific T cells, virus persistence and CMV-associated T cell homeostasis in blood, lymphoid, mucosal and secretory tissues of 44 CMV seropositive and 28 seronegative donors. CMV-specific T cells were maintained in distinct distribution patterns, highest in blood, bone marrow (BM), or lymph nodes (LN), with the frequency and function in blood distinct from tissues. CMV genomes were detected predominantly in lung and also in spleen, BM, blood and LN. High frequencies of activated CMV-specific T cells were found in blood and BM samples with low virus detection, whereas in lung, CMV-specific T cells were present along with detectable virus. In LNs, CMV-specific T cells exhibited quiescent phenotypes independent of virus. Overall, T cell differentiation was enhanced in sites of viral persistence with age. Together, our results suggest tissue T cell reservoirs for CMV control shaped by both viral and tissue-intrinsic factors, with global effects on homeostasis of tissue T cells over the lifespan.

SUBMITTER: Gordon CL

PROVIDER: S-EPMC5339671 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Tissue reservoirs of antiviral T cell immunity in persistent human CMV infection.

Gordon Claire L CL Miron Michelle M Thome Joseph J C JJ Matsuoka Nobuhide N Weiner Joshua J Rak Michael A MA Igarashi Suzu S Granot Tomer T Lerner Harvey H Goodrum Felicia F Farber Donna L DL

The Journal of experimental medicine 20170127 3

T cell responses to viruses are initiated and maintained in tissue sites; however, knowledge of human antiviral T cells is largely derived from blood. Cytomegalovirus (CMV) persists in most humans, requires T cell immunity to control, yet tissue immune responses remain undefined. Here, we investigated human CMV-specific T cells, virus persistence and CMV-associated T cell homeostasis in blood, lymphoid, mucosal and secretory tissues of 44 CMV seropositive and 28 seronegative donors. CMV-specific ...[more]

PMID: 28130404

Similar Datasets

Project description:BackgroundCytomegalovirus (CMV) is one of the most important opportunistic infections in transplant recipients. Currently sero-positivity for CMV IgG before solid organ transplantation is the laboratory test of choice for stratifying the risk of CMV reactivation after solid organ transplantation. Theoretically, CMV-specific cell-mediated immune responses before solid organ transplantation should further categorize patients as high or low risk of CMV development. We therefore evaluated the usefulness of the CMV-specific enzyme-linked immunospot (ELISPOT) assay in kidney transplant (KT) candidates for predicting the development of CMV infections after transplantation.Materials and methodsAll adult CMV IgG (+) recipients admitted to the KT institute between March 2014 and June 2014 were enrolled, and CMV infections after KT were observed between March 2014 and December 2014. All patients underwent CMV pp65 and IE1-specific ELISPOT assays before transplantation. CMV infection was defined in the presence of CMV antigenemia, CMV syndrome, or tissue-invasive CMV disease. We used the data to select optimal cut-off values for pp65 and IE1, respectively, on ROC curves.ResultsA total of 69 transplant recipients involving 54 (78%) living-donor KT, 9 (13%) deceased-donor KT, 3 (4%) kidney-pancreas transplants, and 3 (4%) pancreas transplants were enrolled. Of the 69 patients, 27 (39%) developed CMV infections. There was no association between the IE1-specific ELISPOT assay and CMV infection. However, only 15 (31%) of the 48 patients with positive pp65-specific ELISPOT results (>10 spots/2.0 × 105 cells) developed CMV infections, whereas 12 (57%) of the 21 patients with negative pp65-specific ELISPOT results developed CMV infection (P = 0.04).ConclusionNegative pp65-specific ELISPOT assay results before transplantation appear to predict the subsequent development of CMV infections after transplantation in CMV IgG (+) KT recipients. Therefore, risk stratification of CMV IgG (+) recipients using the CMV-specific ELISPOT, together with preventive strategies, may further reduce CMV development.

Dataset Information

Tissue reservoirs of antiviral T cell immunity in persistent human CMV infection.

Publications

Tissue reservoirs of antiviral T cell immunity in persistent human CMV infection.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets