BACKGROUND: It has been established that the maintenance of immunological tolerance to dietary antigen and the intestinal flora (oral tolerance) is an actively-maintained process dependent upon mucosal lymphocyte populations. Early life exposures appear critical in the development of such tolerance. However little is known about the activation status of mucosal lymphocytes in human infancy and childhood. PATIENTS AND METHODS: We have performed flow cytometric analysis for cell lineage and cytokine-production status in peripheral blood and duodenal intraepithelial lymphocytes taken during endoscopy from 20 children [median age 2.9 +/- 0.6 years (median +/- SE)] in whom investigation found no intestinal abnormalities (histologically normal controls) and 30 children (median age 1.6 +/- 0.4 years) with confirmed allergy to cow's milk and other dietary antigens. RESULTS: Regardless of clinical status, spontaneous production of cytokines was low or undetectable in peripheral blood cells. By contrast, intraepithelial CD4 and CD8 cells isolated from the small intestine were often activated, with 5% or more showing spontaneous production of T(H)1 type [interleukin-2, interferon (IFN)-gamma] cytokines in both normal controls and food-allergic children. Stimulation in vitro strongly induced cytokine production in peripheral blood but not intraepithelial lymphocytes. Immunohistochemistry showed similar density of IFN-gamma(+) intraepithelial lymphocytes in controls and allergic children. CONCLUSIONS: Duodenal intraepithelial lymphocytes in human infants show a state of increased spontaneous activation compared with peripheral blood lymphocytes, and show no significant impairment of T(H)1 responses in food allergic children.
BACKGROUND: It has been established that the maintenance of immunological tolerance to dietary antigen and the intestinal flora (oral tolerance) is an actively-maintained process dependent upon mucosal lymphocyte populations. Early life exposures appear critical in the development of such tolerance. However little is known about the activation status of mucosal lymphocytes in human infancy and childhood. PATIENTS AND METHODS: We have performed flow cytometric analysis for cell lineage and cytokine-production status in peripheral blood and duodenal intraepithelial lymphocytes taken during endoscopy from 20 children [median age 2.9 +/- 0.6 years (median +/- SE)] in whom investigation found no intestinal abnormalities (histologically normal controls) and 30 children (median age 1.6 +/- 0.4 years) with confirmed allergy to cow's milk and other dietary antigens. RESULTS: Regardless of clinical status, spontaneous production of cytokines was low or undetectable in peripheral blood cells. By contrast, intraepithelial CD4 and CD8 cells isolated from the small intestine were often activated, with 5% or more showing spontaneous production of T(H)1 type [interleukin-2, interferon (IFN)-gamma] cytokines in both normal controls and food-allergicchildren. Stimulation in vitro strongly induced cytokine production in peripheral blood but not intraepithelial lymphocytes. Immunohistochemistry showed similar density of IFN-gamma(+) intraepithelial lymphocytes in controls and allergicchildren. CONCLUSIONS: Duodenal intraepithelial lymphocytes in humaninfants show a state of increased spontaneous activation compared with peripheral blood lymphocytes, and show no significant impairment of T(H)1 responses in food allergicchildren.