ABSTRACT
A reduced proliferation to T cell mitogens is observed in vitro in murine cells isolated during the acute phase of Toxoplasma gondii infection. Foxp3(+) regulatory T cells (Tregs) mediate this suppression, which is interleukin (IL)-2 dependent. In this work, we analysed the mechanism of this Treg-mediated suppression. We found that removal of antigen-presenting cells (APC) from spleen cells from infected mice did not modify suppression but further elimination of Tregs led to a restored proliferation, demonstrating that Tregs mediate suppression in the absence of APC. Production of IL-2 by T cells from infected animals was abolished but partially restored when Tregs were removed. However, IL-2 levels and T cell proliferation were restored when Tregs and T cells were separated by transwells, indicating that Tregs require close proximity with T cells to induce suppression. Tregs from infected mice were able to reduce proliferation of CTLL-2 cells in the classical IL-2 bioassay, strongly suggesting that Tregs compete with T cells for IL-2. We found that T cells from infected mice died after a few rounds of division in vitro, but addition of recombinant IL-2 or removal of Tregs abolished this effect. Our results showed that suppression of T cell proliferation during acute Toxoplasma gondii infection is the result of death of proliferating T cells by Treg-mediated IL-2 competition. Thus, immunosuppression is due to death of proliferating T cells as a consequence of low IL-2 availability.
Subject(s)
Cell Proliferation , Interleukin-2/immunology , T-Lymphocytes, Regulatory/immunology , T-Lymphocytes/immunology , Toxoplasmosis/immunology , Animals , Cell Survival/drug effects , Cell Survival/immunology , Female , Flow Cytometry , Fluorescent Antibody Technique , Forkhead Transcription Factors/genetics , Forkhead Transcription Factors/immunology , Forkhead Transcription Factors/metabolism , Green Fluorescent Proteins/genetics , Green Fluorescent Proteins/metabolism , Host-Parasite Interactions/immunology , Interleukin-2/metabolism , Interleukin-2/pharmacology , Mice , Mice, Inbred C57BL , Mice, Transgenic , Spleen/cytology , Spleen/immunology , Spleen/metabolism , T-Lymphocytes/metabolism , T-Lymphocytes, Regulatory/metabolism , Toxoplasma/immunology , Toxoplasma/physiology , Toxoplasmosis/metabolism , Toxoplasmosis/parasitologyABSTRACT
UNLABELLED: This study examines changes in body temperature generated in the wrist area through sensory thermography technique because of highly repetitive movements, proving with this technique that there is a decreased ability to perform muscular work, and thereby assess possible pathologies of Cumulative Trauma Disorders (CTDs). METHODS: Two healthy right-handed individuals, who performed repetitive work, emulating an operation of the textile industry for three days, generated DTA in the area of the wrist. The evaluation time was of 3 hours 30 minutes in a controlled temperature between 20 and 25°C, 20 minutes stabilization time at the beginning and end of the operation. RESULTS: The maximum temperatures reached were on the right wrist (RW) of 35. 078°C over a period of 1 hour 41 minutes 52 seconds; and on the left wrist (LR), 34.663°C over a period of 2 hours 42 minutes 51 seconds, detected discomfort in their right shoulder and wrist in the time range which identified the highest temperatures. It was shown that the data does not fit a normal distribution for RW and LW; the data fit the three- parameters Weibull distribution for WR and LW with a correlation coefficient between 0.93 to 0.99.
