Host Resistance and Immune Deviation in Pigeon CytochromecT-Cell Receptor Transgenic Mice Infected withToxoplasma gondii
| Autor: | Patricia Caspar, George S. Yap, Sara Hieny, Alan Sher, Ronald H. Schwartz, Carla Miller, Carmen M. Collazo |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
CD4-Positive T-Lymphocytes
Male Immunology Receptors Antigen T-Cell Antigens Protozoan Cytochrome c Group Mice Transgenic CD8-Positive T-Lymphocytes Cross Reactions Biology Lymphocyte Activation Microbiology Interferon-gamma Mice Antigen medicine Animals Humans Interferon gamma Columbidae Mice Knockout T-cell receptor Lymphokine Nuclear Proteins Toxoplasma gondii T lymphocyte biology.organism_classification Interleukin-12 Molecular biology Immunity Innate DNA-Binding Proteins Mice Inbred C57BL Infectious Diseases Acute Disease Chronic Disease Interleukin 12 Female Parasitology Interleukin-4 Fungal and Parasitic Infections Toxoplasma Toxoplasmosis CD8 medicine.drug |
| Zdroj: | Infection and Immunity. 68:2713-2719 |
| ISSN: | 1098-5522 0019-9567 |
| Popis: | Resistance toToxoplasma gondiihas been shown to be mediated by gamma interferon (IFN-γ) produced by NK, CD4+, and CD8+T cells. While studies of SCID mice have implicated NK cells as the source of the cytokine in acute infection, several lines of evidence suggest that IFN-γ production by CD4+T lymphocytes also plays an important role in controlling early parasite growth. To evaluate whether this function is due to nonspecific as opposed to T-cell receptor (TCR)-dependent stimulation by the parasite, we have examined the resistance toT. gondiiinfection of pigeon cytochromectransgenic (PCC-Tg) Rag-2−/−mice in which all CD4+T lymphocytes are unreactive with the protozoan. When inoculated with the ME49 strain, PCC-Tg animals exhibited only temporary control of acute infection and succumbed by day 17. Intracellular cytokine staining by flow cytometry revealed that, in contrast to infected nontransgenic controls, infected PCC-Tg animals failed to develop IFN-γ-producing CD4+T cells. Moreover, the CD4+lymphocytes from these mice showed no evidence of activation as judged by lack of upregulated expression of CD44 or CD69. Nevertheless, when acutely infected transgenic mice were primed by PCC injection, the lymphokine responses measured after in vitro antigen restimulation displayed a strong Th1 bias which was shown to be dependent on endogenous interleukin 12 (IL-12). The above findings argue that, whileT. gondii-induced IL-12 cannot trigger IFN-γ production by CD4+T cells in the absence of TCR ligation, the pathogen is able to nonspecifically promote Th1 responses against nonparasite antigens, an effect that may explain the immunostimulatory properties ofT. gondiiinfection. |
| Databáze: | OpenAIRE |
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