Kinetoplastid Biology and Disease

We evaluated the adoptive transfer of DCs on Leishmania (L.) mexicana-infected neonatal BALB/c mice. DCs were isolated and purified from the spleens of the following donor groups: a) Adult BALB/c mice infected during adulthood with L. (L) mexicana; b) Adult BALB/c mice infected during neonatal life; c) Healthy neonatal BALB/c mice; d) Healthy adult BALB/c mice. A neonatal model of infection, generated after inoculation with 5 × 105 promastigotes of L. (L) mexicana, was used as the infection control group. Sixteen hours after intraperitoneal transfer of DCs (1 × 103, 1 × 105, or 1 × 106 cells/ml), neonatal recipient BALB/c mice were infected. The adoptive transfer of DCs diminished disease progression in neonatal mice. This reduction depends on the quantity and provenance of transferred DCs, since the effect was more evident with high numbers of DCs from adult mice infected during adulthood and healthy neonatal mice. Protection was significantly reduced in animals receiving DCs from healthy adult mice but it was absent in mice receiving DCs from adult mice infected during neonatal life. These results suggest that genetic susceptibility to Leishmania infection can be modified during neonatal life, and that the period of life when antigens are encountered is crucial in influencing the capacity of DCs to induce resistance or tolerance. Background Medawar et al. [1] showed almost half a century ago that rodents injected at birth with splenocytes from genetically different donors could accept transplants from that donor as an adult. These milestone experiments guided the notion that the introduction of antigens during neonatal life leads to tolerance and that the immune system functions by making a distinction between self and nonself. For some years, Matzinger et al. have persevered on the hypothesis that tolerance is not an intrinsic property of the newborn immune system [2,3]. For example, many studies have shown that neonatal exposure to antigen may prime T cells and induce both Th1 and Th2 cells [47]. Moreover, Adkins et al. have demonstrated that although neonates develop compartmentally distinct primary responses to antigen immunization (mixed Th1/ Th2 in lymph nodes and Th2 in spleen), after rechallenge the elicited secondary response is always of the Th2 type [7,8]. They have also proved that even in the lymph nodes, the Th2 function persists for a prolonged period after a single immunization, and that animals initially immunized as neonates are impaired in their capacity to Published: 25 January 2005 Kinetoplastid Biology and Disease 2005, 4:2 doi:10.1186/1475-9292-4-2 Received: 01 June 2004 Accepted: 25 January 2005 This article is available from: http://www.kinetoplastids.com/content/4/1/2 © 2005 Ponce et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.