Organ‐Specific Regulation of Interferon‐γ, Interleukin‐2 and Interleukin‐2 Receptor during Murine Infection with Trypanosoma cruzi

Abstract

We have studied the expression of IFN-gamma, IL-2 and IL-2 receptor (IL-2R) at the mRNA and protein levels in spleen and lymph node cells from Trypanosoma cruzi-infected BALB/c mice. At 21 days post infection (dpi) (peak of parasitaemia), spleen cells stimulated with Con A for 16 h showed a reduced IFN-gamma, IL-2 and IL-2R mRNA production compared with non-infected controls. Lymph node cells obtained at 4, 21 or 60 dpi produced similar amounts of IFN-gamma, IL-2 or IL-2R transcripts after mitogen stimulation as uninfected controls. Spleen cells obtained at 21 dpi showed a lower Con A proliferative response and IL-2R expression compared with non-infected controls, while the proliferation and IL-2R expression of lymph node cells at 21 dpi was unaltered. Supernatants from 48 h Con A-stimulated spleen and lymph node cells from mice at 21 dpi had very low levels of IL-2 but contained significantly higher levels of IFN-gamma compared with the supernatants of cells from non-infected mice. The latter phenomenon correlates with an accelerated rate of IFN-gamma mRNA accumulation.

Cytokine Production in Hearts of Trypanosoma cruzi‐Infected CBA Mice: Do Cytokine Patterns in Chronic Stage Reflect the Establishment of Myocardial Pathology?

“…Increased IL-2 production was recorded in the chronic spleen, which would serve to explain cell proliferation (as noted by increased organ size), even in the absence of recorded IFN-production. We have previously demonstrated a differential production of IFN-mRNA in spleen and lymph nodes from Balb/c mice infected with T. cruzi Tulahuén [6]. A recent report accords with this conclusion [41].…”

“…During the chronic stage (>90 dpi) these CBA mice develop a more defined heart disease in which infarctions, fibrosis, calcification and mild inflammation in the enlarged heart are apparent (as compared to C57 Bl/6 or Balb/c (D. Sunnemark, unpublished observations). We have previously reported a high parasitaemia and a transient heart inflammation in Balb/c mice [5,6]. T-cellderived or other cell-derived cytokines (e.g.…”

Administration of anti-CD3 monoclonal antibody during experimental Chagas’ disease induces CD8+ cell-dependent lethal shock

“…In the present model, the very high levels of IFN-induced by the injection of anti-CD3 MoAb are detrimental, as they are involved in the development of a severe shock syndrome. Although our data indicate a major role for CD8 cells in the systemic release of IFN-, they do not exclude the participation of other cell types in the secretion of IFN-in certain lymphoid compartments [32,33]. As a matter of fact, CD3 , CD4 ÿ , CD8 ÿ cells were shown to be involved in the ex vivo secretion of IFN-by spleen cells from T. cruzi-infected mice [4].…”

Characterization of cytokine production in murine Trypanosoma cruzi infection by in situ immunocytochemistry: Lack of association between susceptibility and type 2 cytokine production

“…Because 7: cruzi infects systemically, we feel that the spleen provides the best measure of the immunological status of the infected host and have thus focused our study on cytokine production in this organ. However, it should be noted that cytokine responses to 7: cruzi in other lymphoid compartments [17] and at the sites of infection and disease in the heart (Zhang and Tarleton, in preparation) may differ from that in the spleen.…”