In Vivo Activation of Antigen-Specific CD4 T Cells

Abstract

Physical detection of antigen-specific CD4 T cells has revealed features of the in vivo immune response that were not appreciated from in vitro studies. In vivo, antigen is initially presented to naïve CD4 T cells exclusively by dendritic cells within the T cell areas of secondary lymphoid tissues. Anatomic constraints make it likely that these dendritic cells acquire the antigen at the site where it enters the body. Inflammation enhances in vivo T cell activation by stimulating dendritic cells to migrate to the T cell areas and display stable peptide-MHC complexes and costimulatory ligands. Once stimulated by a dendritic cell, antigen-specific CD4 T cells produce IL-2 but proliferate in an IL-2--independent fashion. Inflammatory signals induce chemokine receptors on activated T cells that direct their migration into the B cell areas to interact with antigen-specific B cells. Most of the activated T cells then die within the lymphoid tissues. However, in the presence of inflammation, a population of memory T cells survives. This population is composed of two functional classes. One recirculates through nonlymphoid tissues and is capable of immediate effector lymphokine production. The other recirculates through lymph nodes and quickly acquires the capacity to produce effector lymphokines if stimulated. Therefore, antigenic stimulation in the presence of inflammation produces an increased number of specific T cells capable of producing effector lymphokines throughout the body.

Distinct in vivo dendritic cell activation by live versus killed Listeria monocytogenes

“…Live and dead L. monocytogenes bacteria localize to distinct splenic regions T cell priming occurs within the splenic white pulp, an area where most T cells are localized [14,15]. Interestingly, live L. monocytogenes rapidly localize to T cell areas of the splenic white pulp following infection with virulent bacteria [6,16].…”

Two-photon tissue imaging: seeing the immune system in a fresh light

“…Jenkins and colleagues 27,47 , among others, have pieced together the time course of the immune response in vivo using a TCR-transgenic mouse system and fluorescence microscopy of fixed tissue sections. However, only recently have attempts been made to image these processes in real time, in intact lymphoid tissues, by two-photon microscopy [48][49][50] and by conventional confocal methodology 51 .…”

Investigating the Immunologic Effects of CoCr Nanoparticles

“…The presence of lymphocytes in perivascular infiltrates surrounding M/M implants suggests activation of CD4+ T helper cells. Naïve, antigen-specific T cells recirculate between the blood and the secondary lymphoid organs where antigen recognition and immune induction occur [9,17]. Activation of T cells is induced by antigen-presenting cells (APCs) that can acquire antigen in tissues and after activation migrate into the draining lymph nodes to interact with recirculating T cells [14].…”

“…Activation of T cells is induced by antigen-presenting cells (APCs) that can acquire antigen in tissues and after activation migrate into the draining lymph nodes to interact with recirculating T cells [14]. Activation of APCs is a central event in initiating adaptive immune responses because in addition to inducing migration, activation of APC also results in increased antigen-presenting activity and importantly, costimulatory activity that generate the appropriate T cell signals, Signal 1 and Signal 2, respectively, required for a productive T cell response [17]. Activation of APCs can be induced by a range of innate stimuli, including exogenous pathogen-associated molecular patterns, endogenous proinflammatory cytokines, and disease-associated molecular patterns (DAMPs) [8].…”

“…Activation of APCs can be induced by a range of innate stimuli, including exogenous pathogen-associated molecular patterns, endogenous proinflammatory cytokines, and disease-associated molecular patterns (DAMPs) [8]. Although studies of APC function have concentrated on dendritic cells (DCs), as a result of their ability to effectively activate naïve, unstimulated T cells [17], B cells can act as potent APCs if activated appropriately [24]. One explanation for the differences in biologic effects between the implants may be the result of the difference in particle sizes shed from these implants, with M/P implants producing micron-sized wear debris as opposed to the nanoparticles produced from M/M articulations [4,6,7].…”