Regulation of Th-1 T cell-dominated immunity to Neisseria meningitidis within the human mucosa.
Neisseria meningitidis is commonly carried asymptomatically in the upper respiratory tract and only occasionally invades the bloodstream and meninges to cause disease. Naturally acquired immunity appears protective but the nature of the cellular immune response within the mucosa is uncertain. We show that following in vitro stimulation with N. meningitidis serogroup B (MenB) antigens, approximately 66% of the dividing mucosal CD4(+)CD45RO(+) memory population express the Th1-associated IL18-R while the remainder express CRTH2, a Th2-associated marker. The pro-inflammatory bias of this anti-MenB response is not evident in blood, demonstrating compartmentalization at the induction site; and occurs in the presence or absence of lipopolysacharide indicating that these responses are already fully committed. Depletion of CD25(+) cells reveals suppression of the effector CD4(+) T cell response restricted to the mucosa and most marked in children (i.e. those at greatest risk of disease). Mucosal T-regulatory cell (Treg) activity is partially overcome by blocking the human glucocorticoid-induced TNF receptor (GITR) and is not seen following stimulation with antigens from another mucosal pathogen, influenza virus. Pro-inflammatory, antimeningococcal T cell responses may limit invasive disease at the mucosa but Treg induction while reducing immunopathological damage, may also restrict the effectiveness of the protective response, particularly in children.
Davenport
Victoria
V
Department of Cellular and Molecular Medicine, School of Medical Sciences, University of Bristol, University Walk, Bristol, UK.
Groves
Eleanor
E
Hobbs
Christopher G
CG
Williams
Neil A
NA
Heyderman
Robert S
RS
D000328:Adult; D000942:Antigens, Bacterial / Q000276:immunology / Q000494:pharmacology; D015704:CD4 Antigens / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D007150:Immunohistochemistry; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D017493:Leukocyte Common Antigens / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009061:Mouth Mucosa / Q000276:immunology*; D009345:Neisseria meningitidis / Q000276:immunology*; D014066:Palatine Tonsil / Q000276:immunology; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology*; D013997:Time Factors
D000942:Antigens, Bacterial; D015704:CD4 Antigens; D053645:Interleukin-2 Receptor alpha Subunit; D017493:Leukocyte Common Antigens