Lymphocyte Function in Experimental African Trypanosomiasis

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Abstract
Cellular mechanisms of immunosuppression were studied in C57BL/6 mice chronically infected with the human pathogen Trypanosoma rhodesiense. Mice lost the capacity to mount primary in vitro splenic PFC responses to sheep erythrocytes (SRBC) within 3 days of infection. The addition of normal mouse spleen cells to infected spleen cell cultures failed to restore responsiveness and, in addition, resulted in the acquisition of unresponsiveness by the normal cells. Parasites present in infected spleen cell cultures were not directly responsible for the suppression observed. Immunosuppression was attributable to suppressor cells present in infected spleens, as assessed by the ability of infected spleen cells to suppress normal spleen cell responses to SRBC. The suppressor cell population could be removed on nylon wool or Sephadex G-10 columns, was insensitive to treatment with anti-Thy 1.2 serum and C, and could be enriched for by adherence to tissue culture dishes. We suggest, therefore, that the splenic suppressor cell is a macrophage. The suppressor macrophage may be present in low concentration within a larger nonsuppressive pool of splenic macrophages since suppressor effects were not evident when <104 adherent cells were transferred to normal cells in dose-response studies. There was good correlation between the appearance of immunosuppression and the presence of suppressor cells in that infected mouse spleen cells exhibited suppressor cell capacity at the time when such cultures became unresponsive to SRBC. Suppressor cells were absent, however, from lymphoid organs other than the spleen, and infected lymph node cell cultures were capable of generating a significant primary in vitro PFC response to SRBC. On the basis of our studies, we suggest that the spleen is the major target organ for immunosuppression in T. rhodesiense infected mice, and that suppression is attributable to the emergence of a suppressor macrophage population that is restricted to the spleen.

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