Suppression of interleukin 2 secretion and interleukin 2 receptor expression during tsetse-transmitted trypanosomiasis in cattle.
Infection with Trypanosoma congolense in cattle was found to be associated with a profound suppression of the host's immune system. Lymph node cells from infected cattle were unable to secrete interleukin 2 (IL 2) in vitro following mitogenic stimulation and the exogenous supply of IL 2 did not restore T cell proliferative responses. This was associated with an impaired expression of the alpha chain of the IL 2 receptor (IL 2R alpha). Co-culture experiments, where cells from an infected animal were mixed with cells from a major histocompatibility complex-matched normal animal, demonstrated the presence of suppressor cells capable of blocking both IL 2 secretion and IL 2R alpha expression. Removal of macrophages by fluorescence-activated cell sorting abrogated suppression in such co-cultures. Following depletion of macrophages, lymph node cells from an infected animal expressed IL 2R alpha at a normal level, but remained incapable of producing IL 2. Hence, the unresponsiveness was associated with macrophage-like suppressor cells which operated at the level of both IL 2 secretion and IL 2R alpha expression, and to an intrinsic unresponsiveness of the T cells which was restricted to IL 2 secretion. Inhibition of prostaglandin synthesis by addition of indomethacin failed to abrogate suppression of either IL 2 secretion or IL 2R alpha expression. This revealed a major difference between the regulation of suppression in murine model infections where the suppression of IL 2 secretion is due to prostaglandin secretion, and the situation in cattle where prostaglandins would not appear to be involved.
Sileghem
M
M
International Laboratory for Research on Animal Diseases (ILRAD), Nairobi, Kenya.
Flynn
J N
JN
D000818:Animals; D002417:Cattle; D006861:Hydrogen Peroxide / Q000378:metabolism; D007108:Immune Tolerance; D007376:Interleukin-2 / Q000378:metabolism*; D008264:Macrophages / Q000502:physiology; D011453:Prostaglandins / Q000502:physiology; D015375:Receptors, Interleukin-2 / Q000032:analysis*; D014348:Trypanosoma congolense; D014353:Trypanosomiasis, African / Q000276:immunology*; D014370:Tsetse Flies / Q000469:parasitology
D007376:Interleukin-2; D011453:Prostaglandins; D015375:Receptors, Interleukin-2; D006861:Hydrogen Peroxide