Mitogenic signal transduction in T lymphocytes in microgravity

Area of Science:

• * Immunology
• * Space Biology
• * Cellular Biology

Background:

• * T cell activation by concanavalin A (Con A) requires accessory cells, such as monocytes.
• * Previous research indicated microgravity inhibits T cell activation in resuspended cultures.
• * The role of accessory cells and microgravity's impact on their function remained unclear.

Purpose of the Study:

• * To investigate the effect of microgravity on human peripheral blood lymphocyte (PBL) activation.
• * To determine the role of monocytes as accessory cells in microgravity.
• * To elucidate the mechanisms underlying altered T cell activation in space.

Main Methods:

• * Human PBLs with monocytes were cultured in microgravity conditions (Spacelab).
• * Cells were either resuspended or attached to microcarrier beads.
• * T cell activation was assessed by [3H]thymidine incorporation, IL-2 and IFN-gamma secretion, and IL-2 receptor expression.

Main Results:

• * Resuspended T cell activation was strongly inhibited in microgravity.
• * T cells attached to microcarrier beads showed more than double the activation in microgravity.
• * Monocyte IL-1 secretion was inhibited in microgravity, while their ultrastructure remained unchanged.
• * IL-2 production appeared independent of IL-1, IL-1 triggered by adhesion, IL-2 receptor expression dependent on IL-1, and activation enhanced with sufficient IL-1.

Conclusions:

• * Microgravity impairs monocyte accessory cell function in resuspended PBL cultures.
• * Cell adhesion to microcarriers is crucial for monocyte IL-1 production and subsequent T cell activation.
• * Microgravity enhances T cell activation when sufficient IL-1 is present, suggesting a complex interplay between adhesion, IL-1, and T cell signaling.
• * Microgravity cultures of PBLs and monocytes offer a model to study accessory cell roles and cell-cell interactions.