Submitted to: Journal of Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/15/2002
Publication Date: 6/15/2002
Citation: Ekkens, M., Liu, Z., Liu, Q., Foster, A., Whitmire, J., Pesce, J., Urban Jr, J.F., Gause, W. Memory th2 effector cells can develop in the absence of b7-1/b7-2, cd28 interactions, and effector t helper cells after priming with an intestinal nematode parasite. Journal of Immunology. 168:6344-6351 (2002) Interpretive Summary: Immunity is characterized by an ability to develop stronger responses to infectious agents that are seen repeatedly. This is the property of memories of an immune response. Memory responses are important because they can respond more quickly to infection and limit the negative affects on the individual. The molecular events that are necessary to trigger immune memory are not well understood, but they are critical for the production of appropriate vaccines against infectious agents, or when the general health of the individual is affected by disease, nutrition, age, or immune deficiency. The current study uses an experimental model of an infection with a gastrointestinal parasite to study the molecules on the surface of immune cells that are thought to regulate both primary and memory responses to infectious agents. The results demonstrate that not all of these surface molecules interact to give the same type of immune memory. There are certain aspects of the immune response that are differentially regulated. Of greater interest is that the immune response is robust in that it can respond to limit the infection even when certain components of the immune response are deficient. This information will help to focus attention on molecules that may be more important in responding appropriately to parasitic infections versus bacterial and viral agents that tend to stimulate different types of immunity.
Technical Abstract: B7-1/B7-2 interactions are required for the development of many Th2-cell mediated primary immune responses including the response that follows infections with the intestinal nematode parasite, Heligmosomoides polygyrus. However, the role of B7-1/B7-2/CD28 interactions in the development of CD4-dependent Th2 memory immune responses is unknown. Following primary inoculation with H. polygyrus, adult worms in the gut were drug-cleared and mice were subsequently challenge-inoculated with H. polygyrus larvae. The memory Th2 response is readily distinguished by a marked reduction in worm egg production that is not observed during the primary response. Following H. polygyrus challenge-inoculation, comparable decreases in egg production and similar increases in mesenteric lymph node cell IL-4 production were observed in Balb/c B7- I/B7-2 negative-and positive mice. However, elevations in the total serum IGGI and IgE levels were reduced, and increases in serum Ag- specific IGGI and germinal center (GC) formation were blocked in H. polygyrus-challenged B7- 1/B7-2 negative mice. In contrast, in H. polygyrus-challenged CD28 negative mice marked elevation in Ag-specific IGGI and increased GC formation were observed. The results demonstrate that effector Th2 memory cells that produce IL-4 and mediate host defense can develop when B7-1/B7- 2 interactions and associated effector Th2 cell development are blocked during priming. However, humoral immunity is differentially affected in B7-1/B7-2 negative and CD28 negative mice following H. polygyrus challenge.