Memory Th2 effector cells can develop in the absence of B7-1/B7-2, CD28 interactions, and effector Th cells after priming with an intestinal nematode parasite.
B7-1/B7-2 interactions are required for many Th2-cell mediated primary immune responses including the response that follows infection with the intestinal nematode parasite, Heligmosomoides polygyrus. However, few studies have examined the role of B7-1/B7-2/CD28 interactions in the development of a Th2 memory immune response. We examined the development of the memory Th2 response to H. polygyrus in BALB/c mice deficient in both B7-1 and B7-2 (B7-1/B7-2(-/-)) and in BALB/c mice deficient in CD28 (CD28(-/-)). Following primary inoculation with H. polygyrus, adult worms in the gut were cleared with an anti-helminthic drug and mice were subsequently challenge-inoculated with H. polygyrus larvae. The memory Th2 response is readily distinguished by its inhibitory effect on adult worm maturation, resulting in marked reductions in adult worm egg production that are not observed during the primary immune 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 B7-1/B7-2(-/-) and B7-1/B7-2(+/+) mice. However, elevations in total serum IgG1 and IgE were reduced, while increases in serum Ag-specific IgG1 and IgE and germinal center formation were blocked in H. polygyrus-challenged B7-1/B7-2(-/-) mice. In contrast, in H. polygyrus-challenged CD28(-/-) mice, marked elevations in Ag-specific IgG1 and IgE and increased germinal center formation were observed. The results of these studies 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 impaired and differentially affected in B7-1/B7-2(-/-) mice and CD28(-/-) mice following H. polygyrus challenge.
Ekkens
Melinda J
MJ
Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
Liu
Zhugong
Z
Liu
Qian
Q
Foster
Anthony
A
Whitmire
Jeannette
J
Pesce
John
J
Sharpe
Arlene H
AH
Urban
Joseph F
JF
Gause
William C
WC
D000818:Animals; D000918:Antibody Specificity / Q000235:genetics; D015703:Antigens, CD / Q000235:genetics* / Q000378:metabolism; D018122:B7-1 Antigen / Q000235:genetics* / Q000378:metabolism; D051940:B7-2 Antigen; D018106:CD28 Antigens / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D018858:Germinal Center / Q000473:pathology; D017099:IgG Deficiency / Q000235:genetics / Q000276:immunology / Q000469:parasitology; D007114:Immunization; D007117:Immunization, Secondary; D007073:Immunoglobulin E / Q000172:deficiency; D007136:Immunoglobulins / Q000096:biosynthesis / Q000097:blood; D007156:Immunologic Memory; D015847:Interleukin-4 / Q000096:biosynthesis; D007411:Intestinal Diseases, Parasitic / Q000235:genetics / Q000276:immunology* / Q000469:parasitology; D008218:Lymphocytosis / Q000276:immunology / Q000469:parasitology; D008231:Lymphopenia / Q000235:genetics / Q000276:immunology / Q000469:parasitology; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009351:Nematospiroides dubius / Q000254:growth & development / Q000276:immunology; D010270:Parasite Egg Count; D017206:Strongylida Infections / Q000235:genetics / Q000276:immunology / Q000469:parasitology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000469:parasitology / Q000473:pathology*; D018418:Th2 Cells / Q000166:cytology* / Q000276:immunology
D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D018106:CD28 Antigens; C497965:Cd86 protein, mouse; D007136:Immunoglobulins; D008562:Membrane Glycoproteins; D015847:Interleukin-4; D007073:Immunoglobulin E