Defective production of and response to IL-2 in acute human falciparum malaria.
Patients with acute Plasmodium falciparum malaria have defective cell-mediated immune responses to malaria-specific Ag (MA). This immunologic defect may partially explain the difficulty with which natural immunity to falciparum malaria develops and may have important implications for the efficacy of potential malaria vaccines in endemic areas. To investigate the basis of this immune defect, we have examined the capacity of PBMC from patients with acute falciparum malaria to produce IL-2 and to express I1-2R in response to Ag stimulation. The effect of exogenous IL-1 and IL-2 on lymphocyte proliferation was studied. Soluble IL-2R levels were measured in acute and convalescent sera. Our results showed that no detectable IL-2 was produced and no IL-2R were expressed by PBMC in response to MA during the acute infection. IL-2 production and IL-2R expression were also depressed when PBMC were exposed to streptococcal Ag. The specific immune defect was not reconstituted by the addition of graded doses of purified human IL-1 or IL-2 and could not be attributed to suppressor adherent cells. In contrast to the absence of IL-2 and cell-bound IL-2R, circulating soluble IL-2R was elevated in acute sera. These findings suggest that the lack of IL-2, through either a defect in its production or inhibition of its activity, may be the basis of the Ag-specific immune unresponsiveness in acute P. falciparum malaria.
Ho
M
M
Hospital for Tropical Diseases, Mahidol University, Bangkok, Thailand.
Webster
H K
HK
Green
B
B
Looareesuwan
S
S
Kongchareon
S
S
White
N J
NJ
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology; D002469:Cell Separation; D006801:Humans; D007108:Immune Tolerance; D007375:Interleukin-1 / Q000494:pharmacology; D007376:Interleukin-2 / Q000096:biosynthesis* / Q000494:pharmacology; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism; D008288:Malaria / Q000097:blood / Q000276:immunology*; D008875:Middle Aged; D010963:Plasmodium falciparum / Q000276:immunology*; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D013299:Streptodornase and Streptokinase / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
D000953:Antigens, Protozoan; D007375:Interleukin-1; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D013299:Streptodornase and Streptokinase