Immune deficiency in chronic Trypanosoma cruzi infection. Recombinant IL-1 restores Th function for antibody production.
Mice with chronic Trypanosoma cruzi infections are unable to mount primary responses to T-dependent Ag, such as SRBC. Responses to SRBC were restored in vitro and in vivo with rIL-1. The cellular basis of the immunodeficiency and the mechanism of IL-1 action were investigated. B cells from infected mice were capable of normal levels of PFC production when provided with the appropriate signals, IL-2 plus IL-1. T cells from infected mice were unable to provide Th function to normal B cells. However, Th activity was provided by these cells if IL-1 was added to the cultures. Furthermore, T-depleted spleen cells from infected mice did not make antibody in the presence of normal T cells unless IL-1 was added to the cultures. Neutralizing antibody against IL-2 greatly reduced the augmentation by IL-1 of the antibody response of cells from infected mice. Together these results indicate that splenic B cells from infected mice are capable of antibody production, but that Th function is lacking in the spleens of infected mice. These results suggest that the inability of mice with T. cruzi infection to mount primary antibody responses to T-dependent Ag may be due to a macrophage defect lending to impairment of Th function. These results document the potential of IL-1 in restoring immune competence in an infectious disease model.
Reed
S G
SG
Seattle Biomedical Research Institute, WA 98109.
Pihl
D L
DL
Grabstein
K H
KH
D000818:Animals; D000910:Antibodies, Heterophile / Q000096:biosynthesis; D000913:Antibodies, Protozoan / Q000096:biosynthesis*; D002469:Cell Separation; D014355:Chagas Disease / Q000276:immunology* / Q000628:therapy; D002908:Chronic Disease; D005260:Female; D006462:Hemolytic Plaque Technique; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000276:immunology* / Q000628:therapy; D007375:Interleukin-1 / Q000008:administration & dosage* / Q000494:pharmacology; D007376:Interleukin-2 / Q000276:immunology; D008211:Lymphocyte Cooperation; D051379:Mice; D008810:Mice, Inbred C57BL; D009500:Neutralization Tests; D011994:Recombinant Proteins / Q000008:administration & dosage* / Q000494:pharmacology; D012756:Sheep; D013154:Spleen; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism
D000910:Antibodies, Heterophile; D000913:Antibodies, Protozoan; D007375:Interleukin-1; D007376:Interleukin-2; D011994:Recombinant Proteins