BothCD4+andCD8+Lymphocytes Participate in the IFN-γ Response to Filamentous Hemagglutinin fromBordetella pertussisin Infants, Children, and Adults

Violette Dirix,Françoise Vermeulen,Virginie Verscheure,Camille Locht,Françoise Mascart,Iris De Schutter,Tessa Goetghebuer

doi:10.1155/2012/795958

Abstract

Infant CD4+ T-cell responses to bacterial infections or vaccines have been extensively studied, whereas studies on CD8+ T-cell responses focused mainly on viral and intracellular parasite infections. Here we investigated CD8+ T-cell responses upon Bordetella pertussis infection in infants, children, and adults and pertussis vaccination in infants. Filamentous hemagglutinin-specific IFN-γ secretion by circulating lymphocytes was blocked by anti-MHC-I or -MHC-II antibodies, suggesting that CD4+ and CD8+ T lymphocytes are involved in IFN-γ production. Flow cytometry analyses confirmed that both cell types synthesized antigen-specific IFN-γ, although CD4+ lymphocytes were the major source of this cytokine. IFN-γ synthesis by CD8+ cells was CD4+ T cell dependent, as evidenced by selective depletion experiments. Furthermore, IFN-γ synthesis by CD4+ cells was sometimes inhibited by CD8+ lymphocytes, suggesting the presence of CD8+ regulatory T cells. The role of this dual IFN-γ secretion by CD4+ and CD8+ T lymphocytes in pertussis remains to be investigated.

Highlights

The immune system of neonates and young infants differs in many aspects from that of adults, which has important implications for the development of effective and safe immuneinterventions and vaccination in early life
As a first approach to analyse the possible contribution of CD4+ and/or CD8+ T lymphocytes in the filamentous hemagglutinin (FHA)-induced IFN-γ production, we analysed the MHC restriction of this IFN-γ secretion by testing the effect of blocking antibodies against the class I and class II MHC molecules
No inhibition was observed for 3 infected children but their FHA-induced IFN-γ secretion was inhibited by the addition of an anti-MHC-I antibody suggesting that in these cases, CD8+ lymphocytes were the predominant IFN-γ producing lymphocyte subset

Summary

Introduction

The immune system of neonates and young infants differs in many aspects from that of adults, which has important implications for the development of effective and safe immuneinterventions and vaccination in early life. Whereas several vaccines administrated during infancy require the development of antigen-specific IFN-γ responses to be protective, the CD4+ T-cell responses in newborns and infants appear to be most often biased towards the Th-2 type. Upon stimulation with the vaccine antigens, the CD4+ T-cell responses are often characterized by the production of IL-4, IL-5, and IL-13 at the expense of IFN-γ [6, 7]. In certain circumstances, even very young infants are able to mount a robust Th-1 type response, with high levels of IFN-γ secretion, and minimal amounts of Th-2 cytokine production. Natural infection with the whooping cough agent Bordetella pertussis

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