The effect of hypogravity and hypergravity on cells of the immune system

Abstract

This article reviews the gravity effects discovered in T lymphocytes and other cells of the immune system. The strong depression of mitogenic activation first observed in an experiment conducted in Spacelab 1 in 1983 triggered several other investigations in space and on the ground in the clinostat and in the centrifuge in the past 10 years. During this period, great progress was made in our knowledge of the complex mechanism of T cell activation as well as the technology to analyze the lymphokines produced during stimulation. Nevertheless, several aspects of the steps leading to activation are not yet clear. Studies in hypogravity and hypergravity may contribute to answering some of the questions. A recent investigation in the U.S. Spacelab SLS-1, based on a new technology in which leukocytes are attached to microcarrier beads, showed that the strong inhibition of activation in microgravity is due to a malfunction of monocytes acting as accessory cells. In fact, interleukin-1 production is nearly nil in resuspended monocytes, whereas T cell activation is doubled in attached cells. In hypergravity, but not at 1g, concanavalin A bound to erythrocytes activates B lymphocytes in addition to T cells. The activation of Jurkat cells is also severely impaired in space. These recent results have raised new questions that have to be answered in experiments to be conducted in space and on Earth in this decade. The experimental system, based on the mitogenic activation of T lymphocytes and accessory cells attached to microcarriers, offers an optimum model for studying basic biological mechanisms of the cell to assess the immunological fitness of humans in space and to test the feasibility of bioprocesses in space as well as on Earth.

Cytoskeleton changes and impaired motility of monocytes at modelled low gravity

“…Especially for T lymphocytes, it is known that exposure of cells in culture to actual or modelled low gravity is often accompanied by a major inhibitory effect, remarkably reducing their mitogenic activation process (Cogoli et al 1984) and severely altering growth rate, cytokine production, gene expression, cytoskeletal structures, and motility (for reviews, see Cogoli 1993Cogoli and Cogoli-Greuter 1997;Lewis 2002;Cogoli-Greuter 2004). Furthermore, it has been demonstrated that human lymphocytes are forced to apoptosis in modelled low gravity, through a pathway based on calciumdependent 5-LOX activation, mitochondrial membrane disruption, and cytochrome c release, followed by caspase activation and cell death (Maccarrone et al 2003).…”

Suppressed PHA activation of T lymphocytes in simulated microgravity is restored by direct activation of protein kinase C

“…Clinostatic rotation is another system that is used to model microgravity for both plant and animal cells [5]. Specifically, clinostats were used to show a suppressed response of lymphocytes to concanavalin A (Con A) that correlated with a suppressed response observed during later orbital flight studies [6][7][8][9]. Clinostats compensate gravity by circular rotation about a horizontal axis, which causes the time-averaged gravitational force to be zero [10].…”

“…Astronauts in-flight of both long-and short-duration missions have a reduced delayed-type hypersensitivity skin test response [15][16][17]. Furthermore, in vitro experiments performed in both true and simulated microgravity demonstrate a suppressed response of lymphocytes to mitogens [6][7][8][9][18][19][20].…”

A review of ground-based heavy-ion radiobiology relevant to space radiation risk assessment. Part II: Cardiovascular and immunological effects

“…Early human studies indicated that space flight changed human cell culture activities, such as leukocyte blastogenesis ( [Cogoli et al, 1980], [Cogoli et al, 1984], [Bechler et al, 1992] and [Cogoli, 1993]), production of cytokines ([Talas et al, 1983] and [Bechler et al, 1992]) and signal transduction in leukocytes ([Limouse et al, 1991] and [Schmitt et al, 1996]). Studies on animal cell cultures have shown alterations in cytokine production (Chapes et al, 1992), and macrophage hematopoiesis and function (Armstrong et al, 1995).…”