Murine schistosomiasis mansoni: coordinate cytokine regulation and differences in cellular immune responses of granuloma cells and splenocytes to endogenous and exogenous schistosome egg antigens
Cl. King et al., Murine schistosomiasis mansoni: coordinate cytokine regulation and differences in cellular immune responses of granuloma cells and splenocytes to endogenous and exogenous schistosome egg antigens, PARASITE IM, 23(11), 2001, pp. 607-615
To better understand the cellular immune mechanisms that regulate granuloma
tous inflammation to Schistosoma. mansoni ova, we examined the dynamics of
lymphocyte proliferation and cytokine expression by granuloma cells and spl
enocytes to endogenous and exogenous schistosome egg antigen (SEA) 6-19 wee
ks postinfection. Compared to splenocytes, granuloma cells (partially CD4() cells) which are at the site of antigen release were highly activated by
endogenous SEA and terminally differentiated as indicated by the more than
10-fold greater frequency of ex vivo interleukin (IL)-4, IL-5 and interfero
n (IFN)-gamma -secreting cells, greater levels of constitutive cytokine pro
duction and failure to proliferate to either endogenous or exogenous SEA. E
ndogenous cytokine production by granuloma cells was coordinately regulated
, enhanced little by exogenous SEA, and temporally correlated with granulom
atous inflammation. By contrast, CD4(+) splenocytes produced comparatively
little cytokine release by endogenous antigen, whereas exogenous SEA strong
ly induced IL-4, IL-5, IL-10 and IFN-gamma production and lymphocyte prolif
eration that correlated poorly with the dynamics of granulomatous inflammat
ion. These results show that cytokine responses to endogenous SEA correlate
d better with granulomatous inflammation than responses to exogenous SEA. F
urthermore, granuloma cells and splenocytes demonstrated strikingly differe
nt proliferative responses and dynamics of cytokine expression, suggesting
that how SEA reactive lymphocytes traffic between lymphoid tissues and the
granuloma is critical to a better understanding of the mechanisms of granul
omatous inflammation and its modulation.