Suppression of antigen-specific T cell proliferation by measles virus infection: role of a soluble factor in suppression

Measles virus infection causes a profound immunosuppression. The basis for this immunosuppression is not known. This immunosuppression could be due to virus acting directly on lymphoid cells, the production of an immunosuppressive viral product, or a lymphoid product. We have developed an antigen-specific T cell system to study measles virus-T-cell interactions. We demonstrate that as few as five infectious viral particles added to 1000 T cells results in profound inhibition of antigen-specific T cell proliferation. Supernates taken from measles virus-infected T cells suppress the proliferation of uninfected T cells. Measles-virus-infected HeLa or Vero cells do not produce the factor. The antiproliferative effects of the supernates cannot be attributed to infectious virus, IL-10 or TGF-beta. The soluble factor appears to be larger than 100 kDa, yet retains antiproliferative activity following trypsin digestion with a size less than 10 kDa. Loss of activity is seen following heat treatment at 56 degrees C. The factor is lymphoid cell specific and exhibits cytokine-like behavior yet appears not to be a known cytokine. This soluble factor may be responsible for the overt clinical immunosuppression seen in man and a previously undescribed cytokine induced by measles virus infection of human lymphocytes.