Abstract
Natural killer (NK) cells contribute to the effector phase of vaccine-induced adaptive immune responses, secreting cytokines and releasing cytotoxic granules. The proportion of responding NK cells varies between individuals and by vaccine, suggesting that functionally discrete subsets of NK cells with different activation requirements may be involved. Here, we have used responses to individual components of the DTP vaccine [tetanus toxoid (TT), diphtheria toxoid (DT), whole cell inactivated pertussis] to characterize the NK cell subsets involved in interleukin-2-dependent recall responses. Culture with TT, DT or pertussis induced NK cell CD25 expression and interferon-γ production in previously vaccinated individuals. Responses were the most robust against whole cell pertussis, with responses to TT being particularly low. Functional analysis of discrete NK cell subsets revealed that transition from CD56bright to CD56dim correlated with increased responsiveness to CD16 cross-linking, whereas increasing CD57 expression correlated with a loss of responsiveness to cytokines. A higher frequency of CD56dim CD57− NK cells expressed CD25 and interferon-γ following stimulation with vaccine antigen compared with CD56dim CD57+ NK cells and made the largest overall contribution to this response. CD56dim CD57int NK cells represent an intermediate functional phenotype in response to vaccine-induced and receptor-mediated stimuli. These findings have implications for the ability of NK cells to contribute to the effector response after vaccination and for vaccine-induced immunity in older individuals.
Highlights
Natural killer (NK) cells are classically regarded as a stable population of innate immune effectors that, by cytokine production or cytotoxicity, help to contain an infection or limit tumour growth until an effective adaptive response is mounted
We have used responses to individual components of the DTP vaccine [tetanus toxoid (TT), diphtheria toxoid (DT), whole cell inactivated pertussis] to characterize the NK cell subsets involved in interleukin-2-dependent recall responses
Functional analysis of discrete NK cell subsets revealed that transition from CD56bright to CD56dim correlated with increased responsiveness to CD16 cross-linking, whereas increasing CD57 expression correlated with a loss of responsiveness to cytokines
Summary
Natural killer (NK) cells are classically regarded as a stable population of innate immune effectors that, by cytokine production or cytotoxicity, help to contain an infection or limit tumour growth until an effective adaptive response is mounted. Antigen-specific memory T cells secreting interleukin-2 (IL-2) promote NK cell function and proliferation, while pathogen-specific antibodies initiate antibody-dependent cellular cytotoxicity by cross-linking CD16 or other Fc receptors for immunoglobulins.[2,3,4,5,6] Alternatively, cytokines released during primary infection may induce NK cells to proliferate and/or differentiate to a more highly responsive state; subsets of NK cells expressing activating receptors able to bind specific pathogen ligands may be responsive (as described for the Ly49H+ subset of mouse NK cells which bind the murine cytomegalovirus m157 protein[7]) Immunology published by John Wiley & Sons Ltd, Immunology, 142, 140–150
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