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 CD25
high
Foxp3
high
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.
Streptococcus pneumoniae
(pneumococcus) is a bacterium that causes pneumonia, meningitis and blood poisoning. Colonization with pneumococcus is common in young children, which may be why they are prone to some common infections such as otitis media (ear infection) and pneumonia. As children age, most develop natural immunity to pneumococcus due to previous colonization. This immunity helps to prevent new infection and/or clear carriage of pneumococcus. However, persistence of carriage occurs in some children. The mechanisms for this are not clear. A good understanding of this phenomenon would help us to develop better ways to prevent pnemococcal infection. We have found that the immune tissues called adenoids (at the back of nose) in children contain some immune cells called “regulatory cells” that inhibit the naturally developed immunity to pnemococcus. While the presence and action of these cells is important to prevent self-tissue damage during infection (due to excessive immune response), they contribute to the persistence of pneumococcal carriage. We show evidence that these cells may develop from the action of some component of pneumococcus. Further studies are underway to determine what component and how it promotes these cells, which may lead to better vaccines to prevent pnemococcus and other similar infections.