Effect of treatment with cyclophosphamide in low doses upon the onset of delayed type hypersensitivity in mice chronically infected with Trypanosoma cruzi: involvement of heart interstitial dendritic cells

Acute infection with Trypanosoma cruzi results in intensemyocarditis, which progresses to a chronic, asymptomatic indeterminate form. Theevolution toward this chronic cardiac form occurs in approximately 30% of allcases of T. cruzi infection. Suppression of delayed typehypersensitivity (DTH) has been proposed as a potential explanation of theindeterminate form. We investigated the effect of cyclophosphamide (CYCL)treatment on the regulatory mechanism of DTH and the participation of heartinterstitial dendritic cells (IDCs) in this process using BALB/c micechronically infected with T. cruzi. One group was treated withCYCL (20 mg/kg body weight) for one month. A DTH skin test was performed byintradermal injection of T. cruzi antigen (3 mg/mL) in thehind-footpad and measured the skin thickness after 24 h, 48 h and 72 h. The skintest revealed increased thickness in antigen-injected footpads, which was moreevident in the mice treated with CYCL than in those mice that did not receivetreatment. The thickened regions were characterised by perivascular infiltratesand areas of necrosis. Intense lesions of the myocardium were present inthree/16 cases and included large areas of necrosis. Morphometric evaluation oflymphocytes showed a predominance of TCD8 cells. Heart IDCs were immunolabelledwith specific antibodies (CD11b and CD11c) and T. cruziantigens were detected using a specific anti-T. cruzi antibody.Identification of T. cruzi antigens, sequestered in these cellsusing specific anti-T. cruzi antibodies was done, showing asignificant increase in the number of these cells in treated mice. These resultsindicate that IDCs participate in the regulatory mechanisms of DTH response toT. cruzi infection.