Immune Activation in Measles

Abstract

Measles is associated with alterations in immune regulation that sometimes lead to secondary infections or autoimmune encephalomyelitis. Simultaneously, an effective measles virus-specific immune response develops. To relate immune activation to measles and its complications, we studied the spontaneous proliferation of blood mononuclear cells and circulating levels of soluble interleukin-2 receptor and CD8 T-cell antigens in 126 patients with complicated or uncomplicated measles at various stages of the disease. Spontaneous proliferation of mononuclear cells, which was present through the first week of the rash, was greater in cells from patients with measles (8787 +/- 1403 cpm) than in those from healthy children (1529 +/- 237 cpm, P less than 0.0001). Levels of soluble interleukin-2 receptor (3385 +/- 195 units per milliliter) and CD8 (4145 +/- 437 units per milliliter) were higher in patients with measles than in those with other infectious diseases (2377 +/- 440, P = 0.003; 2399 +/- 771, P = 0.0374) or in healthy children (865 +/- 138, P less than 0.0001; 1026 +/- 169, P less than 0.0001). Levels of soluble interleukin-2 receptor were elevated before the onset of the rash and remained elevated for several weeks. In contrast, levels of soluble CD8 increased only when the rash appeared, and subsided quickly. Spontaneous proliferation of mononuclear cells and levels of soluble CD8 were similar in patients with uncomplicated disease, pneumonia, or encephalomyelitis, but soluble interleukin-2 receptor levels were lower in patients with encephalomyelitis (2312 +/- 314 vs. 3455 +/- 247 units per milliliter in uncomplicated measles; P = 0.01). In patients with encephalomyelitis, cerebrospinal fluid levels of soluble CD8 (686 +/- 350 units per milliliter), but not interleukin-2 receptor (9 +/- 8.3 units per milliliter), were increased. We conclude that the proliferative phase of the immune response, as measured by the release of soluble interleukin-2 receptor, begins before the rash appears, continues for several weeks in those without complications, but does not occur within the nervous system. In contrast, the effector phase of the immune response, as measured by the release of soluble CD8, coincides with the appearance and disappearance of the rash and occurs within the nervous system during encephalomyelitis.