The role of CD8+ cells in the establishment and maintenance of a Trichuris muris infection.
Chronic infection by the caecal-dwelling intestinal murine nematode Trichuris muris occurs if given as a high-dose infection to 'susceptible' AKR mice or as a low-dose infection to the normally 'resistant' C57BL/6 mouse strain. Both regimes result in a type 1 cytokine response, i.e. high levels of IFN-gamma and IL-12. Here we show this susceptible response is associated with a large population of CD8(+) IFN-gamma(+) cells within the mesenteric lymph nodes and numerous CD8(+) cells infiltrating the caecal mucosa. Despite this, the in vivo abolition of CD8(+) cells within AKR and C57BL/6 mice, either prior to infection or once infection has become established, failed to affect chronicity, implying that CD8(+) T cells are not essential for the initiation or maintenance of the susceptible response to T. muris. Interestingly, the percentage of IFN-gamma(+) CD4(+) cells increased in treated groups, perhaps in a compensatory role. The majority of antigen-specific cytokine responses were comparable in both treated and control groups, although IL-5 was fivefold higher in animals receiving anti-CD8 mAbs and IFN-gamma was also raised in treated mice. Mastocytosis was unaltered by CD8 depletion, however, paradoxically, eosinophilia within the caecum was reduced in treated mice. Together these data clearly demonstrate that CD8(+) T cells are associated with chronic T. muris infection; however, these cells are dispensable for both the early and late phases of this response, but do appear to play a role in the regulation of certain cytokines and caecal eosinophilia.
Humphreys
N E
NE
School of Biological Sciences, University of Manchester, UK. neil.e.humphreys@man.ac.uk
Worthington
J J
JJ
Little
M C
MC
Rice
E J
EJ
Grencis
R K
RK
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002432:Cecum / Q000276:immunology / Q000469:parasitology; D002908:Chronic Disease; D007371:Interferon-gamma / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D008806:Mice, Inbred AKR; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D014257:Trichuriasis / Q000276:immunology* / Q000469:parasitology / Q000503:physiopathology*; D014258:Trichuris / Q000472:pathogenicity*
D015848:Interleukin-5; D007371:Interferon-gamma