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Nippostrongylus infection strongly stimulates TH2 activity in vivo. Given the evidence of cross regulation between TH2 and TH1 cells, and the link between TH1 activity and graft rejection, we examined the effects of Nippostrongylus infection on the fate of kidney allografts in rats. Both prior Nippostrongylus infection and prior treatment with a soluble worm product significantly delayed kidney allograft rejection. Control graft rejection occurred at 9.7 +/- 1.2 days whereas grafts in Nippostrongylus- or worm extract-treated recipients lasted 32.7 +/- 11.3 days and 21.5 +/- 4.6 days, respectively. At day 5 posttransplant mononuclear cell infiltration was much reduced in the Nippostrongylus-treated recipients. Flow cytometry of isolated graft-infiltrating leukocytes showed a marked decrease in infiltrating T cells (82.8% reduction) with both CD4+ cells (81.0% reduction) and CD8+ cells (84.6% reduction) being reduced. CD8+ T cells, in particular, made up a much smaller proportion of the graft-infiltrating cells (22% rather than 49%) in the Nippostrongylus-treated animals as compared with untreated controls. Immunohistochemical assay of the graft tissue confirmed the flow cytometric results. Interleukin 4 expression was clearly demonstrated by RT-PCR of the isolated graft-infiltrating leukocytes from the Nippostrongylus-treated recipients but not from the control recipients. These data are consistent with our current hypothesis that Nippostrongylus delays graft rejection by inducing a cross-regulatory suppression of TH1 activity.

Exposure to environmentally and occupationally encountered toxicants can be associated with the development of certain autoimmune diseases and with the induction of antinuclear antibodies (ANA). Some chemicals used in the agricultural industry are known to affect immune function but their roles in the induction of autoimmunity in general, and ANA in particular, have not been reported previously. This study was undertaken to establish the prevalence of ANA in a rural population and to determine environmental and occupational exposures with which they are associated. This cross-sectional study represented one component of an interdisciplinary project (Prairie Ecosystem Study [PECOS], Eco-Research Program, Tri-Council Secretariat of Canada) designed to explore, in a rural population, the roles of environmental exposures as determinants of human health status. Information regarding lifetime, current, and main occupational exposures in the rural-dwelling study population was derived from a self-administered questionnaire. Sera from consenting subjects, collected during the months of February and March 1996, were assayed for ANA by indirect immunofluorescence on HEp-2 cells. The study population comprised 322 adult subjects (mean age 49.3+/-14.7 yr; range 16-87 yr). Statistical analyses adjusted for age and sex revealed that the presence of ANA among the participants was associated with a current agricultural occupation that included oilseed production, hog production, or poultry production. There was a significant association between ANA positivity and a current main farming operation of crop production. There was also an association among individual participants between lifetime exposure to the insecticide class of pesticides and the presence of ANA. In this rural study population, ANA positivity was significantly associated with lifetime exposure specifically to carbamate, organochlorine (including aldrin, chlordane, dieldrin, endrin, heptachlor, and lindane, but excluding DDT and methoxychlor), and pyrethroid insecticides and to phenoxyacetic acid herbicides, including 2,4-D. After adjustment for age, sex, and other insecticide exposures, multivariate analyses indicated that ANA positivity was associated with current oilseed production and with lifetime exposure to pyrethroid insecticides. In a rural population, ANA were associated with production of certain crops and certain animals and exposure to specific pesticides. The data indicate that some occupational exposures related to the agricultural industry are associated with the presence of ANA, a serologic expression of autoimmunity.

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