Impaired protective immunity and T helper 2 responses in alymphoplasia (aly) mutant mice infected with Trichinella spiralis

Abstract

SUMMARYThe alymphoplasia (aly) mutation of mice prevents the development of systemic lymph nodes and Peyer's patches. The mutant homozygotes (aly/aly) are partially de®cient in both humoral and cellmediated immune functions. In the present study, we show that adult worm expulsion was slightly delayed and that T helper 2 (Th2)-type responses were partially defective in aly/aly mice after infection with Trichinella spiralis. Male aly/aly and aly/+ mice (8-weeks old) were infected with 400 muscle larvae. There was no difference in worm recovery between the two groups on day 5. However, worm recovery in aly/aly mice was signi®cantly higher than that in aly/+ mice on day 14. Mucosal mast cells increased in number and peaked 14 days after infection in aly/+ mice. aly/aly mice were de®cient in their mucosal mast cell response through out the primary infection. To examine the existence of mast cell precursors, aly/aly mice were treated with recombinant interleukin-3 (rIL-3) before infection. The mast cell response was poorly induced in aly/aly mice treated with rIL-3. An immunoglobulin E (IgE) response was not detected in aly/aly mice during the course of infection. Serum IgG1 levels in aly/aly mice were signi®cantly lower than that of aly/+. The serum IgG2a levels increased in both strains of mice. However, IgG2a production in aly/aly mice on day 14 was half as much as that in aly/+mice. Stimulation of splenic T cells in vitro with anti-CD3 monoclonal antibody (mAb) showed that spleen cells from aly/+ mice on day 5 produced more IL-4 than spleen cells from aly/aly mice. IL-4 production from aly/aly mice on day 14 was half that from aly/+ mice. Interferon-c (IFN-c) was produced in both aly/aly and aly/+ mice on day 14. Proliferation assay showed that T cells of aly/aly mice responded poorly when cultured with antigen-presenting cells. These results suggest that aly gene is needed for the induction of protective immunity and Th2 responses in mice infected with T. spiralis.

The nonsense-mediated RNA decay pathway is disrupted in inflammatory myofibroblastic tumors

“…As evidence that this model applies in vivo, RT-qPCR analysis revealed upregulated expression of the chemokine genes IL-8, CCL20, and CXCL1 in the patient 15 IMT relative to NT ( Figure 3C). Another property of NIK is its ability to promote B cell proliferation and induce B cells to differentiate into IgE-secreting plasma cells (12,13). The commitment of a B cell to isotype class switch to an IgEproducing cell requires induction of Cε germline transcription (14,15).…”

NF-κB–inducing kinase controls lymphocyte and osteoclast activities in inflammatory arthritis

“…Thus, the failure of Nik -/-mice to respond to AIA is due to T cell dysfunction. Furthermore, although other model systems have shown at least partial immune reactions in NIK-deficient mice (21)(22)(23), the complete resistance of Nik -/-mice to this arthritis model is unique.…”

“…Thus, the presence of lymph nodes is not required for the induction of AIA. Nevertheless, the lack of lymph nodes in Nik -/-mice might contribute to their failure to respond to mBSA challenge, in combination with the lymphocyte defects (21,23,43). In order to evaluate the capacity of Nik -/-cells to confer susceptibility to AIA in the presence of a normal lymph node stroma, we transferred unfractionated splenocytes (containing a mixture of T cells, B cells, and APCs) or mixtures of purified T and B cells, into syngeneic Rag2 -/-hosts.…”

“…NIK-deficient mice lack peripheral lymph nodes and Peyer's patches, due to defects in the stromal cell response to Lt-β (18)(19)(20). In intact NIK-deficient animals, this stromal cell abnormality also contributes to lymphocyte dysfunction, with decreased antibody production after immunization (18) and delayed clearance of pathogens (21,22). Bone marrow transplant experiments have demonstrated cell-autonomous defects in lymphocytes, including decreased proliferation of both B and T cells and reduced antibody production, although the degree of dysfunction depends on the mode of stimulation and the specific function assayed (23).…”

Th17 cells influence intestinal muscle contraction during Trichinella spiralis infection

“…30770986). tion during and after infection of Trichinella spiralis [7][8][9] , it is unknown about the functionality of Th17 in this process. Previously, TGF-β1 has been commonly considered to be an anti-inflammatory cytokine [10] , It is now found to be critical in the differentiation of Th17 cells [11] .…”