Depletion of T-cell subpopulations results in exacerbation of myocarditis and parasitism in experimental Chagas' disease.
The contribution of T-cell subpopulations to immunopathology in murine Trypanosoma cruzi infection was studied by using in situ localization of lymphocytes and in vivo depletion of T-lymphocyte populations. CD8+ T cells were the major lymphocyte population in the inflamed hearts of C3H/HeSnJ mice infected with the Sylvio X10/4 clone of T. cruzi at all time points of the acute and chronic phases of the infection examined. Depletion of CD8+ and/or CD4+ T cells beginning on day 20 of the infection resulted in a moderate decrease in the inflammation and an increase in parasite burden in the hearts of mice at day 30 of infection. Longer-term depletion, beginning at day 20 and extending as long as 200 days of infection, resulted in an increased inflammatory response in the heart. A large proportion of the inflammatory cells in the hearts of anti-CD8- or anti-CD4- and anti-CD8-treated mice were Thy1+ and CD4- CD8-. At 200 days of infection, the increased inflammation was accompanied by an increase in the parasite load in the heart. These results show that T-cell subset depletion does not prevent the inflammatory response associated with acute and chronic T. cruzi infection. The increased parasite load in T-cell-depleted mice also demonstrates the participation of these T-cell subsets in regulation of parasite load throughout the course of the infection. The increased inflammatory response despite T-cell depletion and in association with increased numbers of tissue parasites suggests that intracellular parasites are a driving force behind the inflammatory response in chronic murine T. cruzi infection.
Tarleton
R L
RL
Department of Zoology, University of Georgia, Athens 30602.
Sun
J
J
Zhang
L
L
Postan
M
M
D000818:Animals; D002598:Chagas Cardiomyopathy / Q000209:etiology* / Q000276:immunology / Q000469:parasitology; D005260:Female; D006321:Heart / Q000469:parasitology*; D008212:Lymphocyte Depletion; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009205:Myocarditis / Q000209:etiology*; D016176:T-Lymphocyte Subsets / Q000502:physiology*