Differential response of T cells to an immunogen, a mitogen and a chemical carcinogen in a mouse model system

Abstract

In this study, we examined the relative immune response of T-lymphocytes and its intracellular cholesterol homeostasis, in a mouse model system, after treatment with immunogen, mitogen, and carcinogen. We studied the T-lymphocyte percentage, their LDL-receptor expression, along with the levels of serum interleukins (IL-2, IFNγ, IL-4, and IL-10) and intracellular cholesterol concentration (cytoplasmic and nuclear). The mitogen was found to be a better stimulator of T-cell marker expressions than the immunogen; though the immunogen was more effective on immunogenic response as was marked from interleukin levels. The chemical carcinogen benzo-α-pyrene at low concentration acted potentially like a mitogen but a reduced immune response was apparent at a carcinogenic dose.The findings in our study focus on the effect of carcinogenic dose of benzo-α-pyrene (BaP) on T-cell immunity. Benzo-α-pyrene causes immunosuppression through restriction of the T-cell population by targeting intracellular cholesterol. K E Y W O R D S benzo-alpha-pyrene, cholesterol, cytokines, LDL receptor, pokeweed mitogen, T cells, tetanus toxoid J Biochem Mol Toxicol. 2019;33:e22290.wileyonlinelibrary.com/journal/jbt Differential response of T cells to an immunogen, a mitogen and a chemical carcinogen in a mouse model system.

Atherosclerosis and carcinoma: Two facets of dysfunctional cholesterol homeostasis

“…[38] Also, we could show the intracellular cholesterol deficiency as a function of immune cell death in the precancerous state. [40,41] As a result, foreign procarcinogens can accumulate in a systemic environment before their activation F I G U R E 2 A, Benzodiazepine receptor (peripheral benzodiazepine receptor): a cholesterol receptor cum channel. B, Ligand (carcinogen)mediated signaling by the aryl hydrocarbon receptor (AhR).…”

“…[ 38 ] Also, we could show the intracellular cholesterol deficiency as a function of immune cell death in the precancerous state. [ 40,41 ] As a result, foreign procarcinogens can accumulate in a systemic environment before their activation into active carcinogens to drive aggressive tumorigenic cell proliferation. It remains still unexplored whether a feed‐forward mechanism of cholesterol transport through these two nuclear surface proteins, PBR and AhR, in the presence of carcinogens is responsible to upset the tidiness of DNA replication resulting in tumor generation from uncontrolled cell multiplication.…”

“…Recent work in our laboratory also monitored the impact of cholesterol in cell cycle operation [38,39] and cancer cell progression. [40][41][42][43][44][45] In cancer tumor cells, the cholesterol pool is not under the control of intracellular sterol regulatory element-binding protein (SREBP)-mediated feedback regulation [46][47][48] to maintain cholesterol homeostasis [49] and gets accumulated within cell nucleus by crossing the nuclear membrane possibly through peripheral type benzodiazepine receptor and promotes cell proliferation. [38,44,50,51] In the precancerous stage, the immune cells also die because of a lack of requisite concentration of cytosolic and nuclear cholesterol in the intracellular pool, [40,41] preferably from the interference of cholesterol transport by carcinogens across the nuclear membrane.…”