Differentially enhanced cytokine gene expression in CD4⁺ and CD8⁺ T cells in mesenteric lymph nodes in rats infected with Nippostrongylus brasiliensis

Abstract

Autoinfective strongyloidiasis is potentially fatal, yet the majority of infected individuals harbour asymptomatic and chronic infections. The role of humoral responses in modulating autoinfection was assessed by examining antibody isotype responses to filariform larval antigens amongst chronically infected ex-Far East Prisoners of War (exFEPOWs) with longstanding (> 30 years) infection. Serum immunoglobulin (Ig)G1, IgG4, IgE and IgA responses to whole Strongyloides stercoralis L3 extracts and their constituent antigenic components were characterized by ELISA and quantitative immunoblotting. Comparison of two groups of S. stercoralis infected exFEPOWs with and without detectable larvae in stool demonstrated novel trends. Significantly enhanced recognition of six immunodominant antigenic components by IgA was associated with undetectable larval output, as was enhanced IgE recognition of several components. Additionally, IgE and IgG4 exhibited parallel antigen recognition patterns. These findings are consistent with roles for IgA in modulating larval output, for IgE in regulating autoinfection, and for IgG4 in blocking IgE-mediated responses in human strongyloidiasis.

Suppression of Gamma Interferon Transcription and Production by Nematode Excretory-Secretory Antigen during Polyclonal Stimulation of Rat Lymph Node T Cells

“…Certain helminth infections induce strong type 2 immune responses, such as elevation of total serum IgE, intestinal mastocytosis, and peripheral eosinophilia in humans, mice, and rats (4,11,12,24,25,27,28). ES antigen derived from N. brasiliensis enhanced IL-4 production by MLN cells from infected rats (R. Uchikawa et al, unpublished data), and intraperitoneal injection of the antigen induced the elevation of total IgE in naive rats (27).…”

“…After discontinuous Ficoll gradient centrifugation, mononuclear cells from two or three rats were pooled and suspended in Hanks balanced salt solution containing 5% fetal calf serum. CD4 ϩ and CD8 ϩ T cells were purified from MLN cells by negative selection as described previously (12). In brief, MLN cells were incubated for 30 min on ice with a mixture of the following mouse monoclonal antibodies: anti-rat CD45RA, specific for B cells (OX-33; Serotec, Oxford, United Kingdom), and anti-rat CD8 (OX-8; Serotec) for CD4 ϩ T-cell selection or anti-rat CD45RA and anti-rat CD4 (W3/25; Serotec) for CD8 ϩ T-cell selection.…”

“…Proliferation of ConAstimulated MLN cells was determined by the relative incorporation rate of RT-PCR. The levels of IL-4 and IFN-␥ mRNA expression were analyzed by reverse transcription (RT)-PCR as described previously (11,12). Briefly, RNA extracted from cultured MLN cells was reverse transcribed in reverse transcriptase buffer containing oligo(dT) primer (Pharmacia, Uppsala, Sweden), RNase inhibitor (Toyobo, Osaka, Japan), deoxynucleoside triphosphate, dithiothreitol, and Superscript II reverse transcriptase (Gibco BRL).…”

“…Infection by intestinal nematodes, such as Heligmosomoides polygyrus, Nippostrongylus brasiliensis, and Trichinella spiralis, induces Th2-skewed immune responses which are closely associated with worm rejection (24,29). N. brasiliensis infection induces dramatic increases of IL-3, IL-4, IL-5, and IL-13 gene expression together with immunoglobulin E (IgE) antibody production and mucosal mastocytosis (11,12,25). Finkelman et al reported that IL-12 administration in N. brasiliensis-infected mice suppressed type 2 responses and enhanced adult worm survival and egg production, while anti-IFN-␥ antibody inhibited the effects of IL-12, suggesting that not only IL-12 but also IFN-␥ levels during the initiation of immune responses are critical for the development of type 1 or type 2 responses (5).…”

Major histocompatibility complex (MHC) class II but not MHC class I molecules are required for efficient control of Strongyloides venezuelensis infection in mice

“…Subsequently, in the peripheral tissues, the immune response against foreign antigens, for example in helminth infections, involves the interaction of peptide–MHC class II complexes with CD4 + T cells, 12 which differentiate into Th2 lymphocytes and provide the basis for the protection against the nematode infection 13–16 . Conversely, the interaction between peptide–MHC class I complexes and CD8 + T cells seems to be involved in the suppression of immune responses in chronic helminthiasis 17,18 . In MHC class I deficient (MHC I −/− ) mice, which are unable to express β2 microglobulin, infection with Nippostrongylus brasiliensis induces an intact Th2 response, 19 while MHC II −/− mice are completely susceptible to this worm 14,15 .…”