Abstract
Regulatory T cells (Treg) diminish immune responses to microbial infection, which may contribute to preventing inflammation-related local tissue damage and autoimmunity but may also contribute to chronicity of infection. Nasopharyngeal carriage of pneumococcus is common in young children and can persist for long periods but it is unknown whether the presence of Treg in the nasopharynx contributes to this persistence. We have investigated the numbers and activities of Foxp3+Treg in adenoidal tissues and their association with pneumococcal carriage in children. Expression of Treg cell-related markers including Foxp3, CD25, CD39, CD127 and CLTA4 were analysed by flow-cytometry in adenoidal mononuclear cells (MNC) and PBMC from children. Unfractionated MNC or Treg-depleted MNC were stimulated with a pneumococcal whole cell antigen (WCA) and T cell proliferation measured. Cytokine production by MNC was measured using a cytometric bead array. Higher numbers of CD25highFoxp3high Treg expressing higher CD39 and CTLA4 were found in adenoidal MNC than in PBMC. Children with pneumococcus positive nasopharyngeal cultures had higher proportions of Treg and expressed higher levels of CD39 and CTLA-4 than those who were culture negative (−). WCA induced adenoidal Treg proliferation which produce IL10 but not IL17, and CD4 T cell proliferation in Treg-depleted MNC was greater in pneumococcal culture positive than negative children. Significant numbers of Treg with an effector/memory phenotype which possess a potent inhibitory effect, exist in adenoidal tissue. The association of pneumococcal carriage with an increased frequency of adenoidal Treg suggests that Treg in nasal-associated lymphoid tissue (NALT) may contribute to the persistence of pneumococcus in children. Further studies to determine what component and mechanisms are involved in the promotion of Treg in NALT may lead to novel therapeutic or vaccination strategy against upper respiratory infection.
Highlights
Regulatory T cells (Treg) play a key role in the control of various aspects of the immune response including maintenance of immune tolerance and prevention of autoimmunity [1]
Numbers of Treg and their expression of activation markers in adenoidal tissue The numbers of Treg in both peripheral blood mononuclear cells (PBMC) and adenoidal mononuclear cells (MNC) were counted by staining for intracellular Foxp3 and/or CD4, CD25 and CD127
Foxp3+ Treg can be divided into naıve and effector/memory phenotypes according to the expression of CD45RA or RO, CD69 and CD25 [30]
Summary
Regulatory T cells (Treg) play a key role in the control of various aspects of the immune response including maintenance of immune tolerance and prevention of autoimmunity [1]. Intracellular expression of Foxp is still considered the most specific single marker of Treg, a combination of phenotypic expression of CD4+CD25+CD127low has been established as a useful marker for natural Treg [4,5] Some phenotypic markers such as CD39 and CTLA-4 have been found to be associated with the activity of Treg [6,7,8,9]. It has been suggested that Treg can be activated and expanded against a wide range of different pathogens in vivo Such pathogen-specific Treg may prevent the infection-induced immunopathology but may prolong pathogen persistence by inhibiting protective immunity favoring chronicity of infections [12]. Treg may contribute to the immunopathogenesis of chronic infections including Human Immunodeficiency virus (HIV), Hepatitis C virus (HCV) and
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