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Frequency and phenotype of natural killer cells and natural killer cell subsets in bovine lymphoid compartments and blood.

ABSTRACT: Natural killer (NK) cells are widely distributed in lymphoid and non-lymphoid tissues, but little is known about the recirculation of NK cells between blood and tissues. This is relevant to understanding recirculation in the steady-state and also for determining the roles for NK cells in vaccine-induced immunity and responses to infection. Therefore, the percentage of NK cells and their phenotype across peripheral blood, afferent lymph and lymph nodes in steady-state conditions was investigated in cattle using the pseudo-afferent lymphatic cannulation model. CD2⁺ CD25^lo NK cells were the predominant subset of NK cells within the blood. In contrast, CD2^- CD25^hi NK cells were the main subset present within the skin-draining afferent lymphatic vessels and lymph nodes, indicating that CD2^- NK cells are the principal NK cell subset trafficking to lymph nodes via the afferent lymphatic vessel. Furthermore, a low percentage of NK cells were present in efferent lymph, which were predominantly of the CD2^- subset, indicating that NK cells can egress from lymph nodes and return to circulation in steady-state conditions. These compartmentalization data indicate that NK cells represent a population of recirculating lymphocytes in steady-state conditions and therefore may be important during immune responses to vaccination or infection.

SUBMITTER: Hamilton CA

PROVIDER: S-EPMC5382329 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Frequency and phenotype of natural killer cells and natural killer cell subsets in bovine lymphoid compartments and blood.

Hamilton Carly A CA Mahan Suman S Bell Charlotte R CR Villarreal-Ramos Bernardo B Charleston Bryan B Entrican Gary G Hope Jayne C JC

Immunology 20170207 1

Natural killer (NK) cells are widely distributed in lymphoid and non-lymphoid tissues, but little is known about the recirculation of NK cells between blood and tissues. This is relevant to understanding recirculation in the steady-state and also for determining the roles for NK cells in vaccine-induced immunity and responses to infection. Therefore, the percentage of NK cells and their phenotype across peripheral blood, afferent lymph and lymph nodes in steady-state conditions was investigated ...[more]

PMID: 28063176

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Project description:BackgroundAnti-CD19 chimeric antigen receptor (CAR) T-cell therapy has shown remarkable clinical efficacy in B-cell cancers. However, CAR T cells can induce substantial toxic effects, and the manufacture of the cells is complex. Natural killer (NK) cells that have been modified to express an anti-CD19 CAR have the potential to overcome these limitations.MethodsIn this phase 1 and 2 trial, we administered HLA-mismatched anti-CD19 CAR-NK cells derived from cord blood to 11 patients with relapsed or refractory CD19-positive cancers (non-Hodgkin's lymphoma or chronic lymphocytic leukemia [CLL]). NK cells were transduced with a retroviral vector expressing genes that encode anti-CD19 CAR, interleukin-15, and inducible caspase 9 as a safety switch. The cells were expanded ex vivo and administered in a single infusion at one of three doses (1×105, 1×106, or 1×107 CAR-NK cells per kilogram of body weight) after lymphodepleting chemotherapy.ResultsThe administration of CAR-NK cells was not associated with the development of cytokine release syndrome, neurotoxicity, or graft-versus-host disease, and there was no increase in the levels of inflammatory cytokines, including interleukin-6, over baseline. The maximum tolerated dose was not reached. Of the 11 patients who were treated, 8 (73%) had a response; of these patients, 7 (4 with lymphoma and 3 with CLL) had a complete remission, and 1 had remission of the Richter's transformation component but had persistent CLL. Responses were rapid and seen within 30 days after infusion at all dose levels. The infused CAR-NK cells expanded and persisted at low levels for at least 12 months.ConclusionsAmong 11 patients with relapsed or refractory CD19-positive cancers, a majority had a response to treatment with CAR-NK cells without the development of major toxic effects. (Funded by the M.D. Anderson Cancer Center CLL and Lymphoma Moonshot and the National Institutes of Health; ClinicalTrials.gov number, NCT03056339.).

Dataset Information

Frequency and phenotype of natural killer cells and natural killer cell subsets in bovine lymphoid compartments and blood.

Publications

Frequency and phenotype of natural killer cells and natural killer cell subsets in bovine lymphoid compartments and blood.

Similar Datasets

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