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.
Treatment with recombinant interleukin–3 (rIL–3) augmented IL–4 production of spleen cells in mice infected with Trichinella spiralis. In a previous report, we showed that treatment with rIL–3 accelerated IgE responsiveness in mice. We have examined IL–4 and interferon (IFN)–γ production by spleen cells from both rIL–3–treated and untreated mice during the early stages of infection. The results indicated that IL–4 production was enhanced in rIL–3–treated mice compared to that in untreated mice. In contrast, there was no difference in IFN–γ production between the two groups. Augmentation of IL–4 production was dependent on the dose of rIL–3 injected before infection. To examine if the treatment with rIL–3 affects T cell function, spleen cells from mice treated with various doses of rIL–3 were cultured under the stimulation with anti–CD3 (T cell receptor complex) mAb and then assessed for cytokine production. IL–4 production increased depending on the dose of rIL–3, while IFN–γ production did not. Furthermore, spleen cells were separated by surface markers, Thy1.2, CD4 and CD8. Thy1.2+ cell population responded significantly to produce IL–4 after anti–CD3 stimulation, when compared with IL–4 production of Thy1.2– cell population. A major producer of IL–4 in T cells was CD4+ cell population but not CD8+ cell population. IL–4 production was suppressed in rIL–3–treated mice injected with anti–CD4 mAb. These results suggest that IL–3 might play a role as Th2 amplifier in immune response to parasite infection.
The response of tumour necrosis factor (TNF)-sensitive murine L929 cells to TNF was enhanced approximately 1000-fold after step-down heating (SDH) for 30 min at a sensitizing temperature (ST) of 43 degrees C and a subsequent 24 h incubation at a test temperature (TT) of 40.5 degrees C, compared to continuous treatment at 37 degrees C. The TNF-resistant phenotype of murine EMT-6 mammary adenocarcinoma cells could be overcome by 24 h heating at a TT of 40.5 degrees C, and their sensitivity to TNF could be further increased by preheating at the ST for up to 60 min. The response of TNF-sensitive HCT-15 human colon adenocarcinoma cells was somewhat similar to that of L929 cells except that there was u approximately 2.5 log increase in TNF-sensitivity due solely to heating at 40.5 degrees C. The response of TNF-resistant DLD-1 human colon adenocarcinoma cells was similar to that of EMT-6 cells. In contrast, three normal cell lines demonstrated greater resistance to any TNF/SDH treatment examined. Our results suggest that SDH may overcome the resistance or enhance the response of tumour cells to TNF while minimizing cytotoxic effects on normal cells.
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