A virus-sensitive suppressor cell is involved in the regulation of human allospecific T cell-mediated cytotoxicity.
The in vitro generation of allospecific CTL by human PBMC was enhanced 4- to 16-fold by sequential plastic and nylon wool adherence, which depleted the PBMC of macrophages and B cells. The enhanced CTL response was suppressed by adding back irradiated, unfractionated PBMC or adherent cells to the depleted cells. This finding suggests that the enhanced CTL response was not simply a consequence of enrichment of T cells, but was instead due to active suppression by radioresistant cells contained in the adherent fraction. Of note is the finding that, unlike the CTL response, the proliferative response to allostimulation was not affected by the removal of adherent cells. The suppressor function could be abrogated by preincubation of irradiated PBMC with influenza A virus before the coculture with depleted cells. Furthermore, costimulation of unfractionated PBMC with influenza A virus and allogeneic stimulators augmented allospecific CTL activity. Thus, in the adherent fraction of human PBMC, there appears to be a native suppressor population that can be functionally inactivated by virus. This result may account for the clinical observation of increased allograft rejection after certain viral infections.
Muluk
S C
SC
Experimental Immunology Branch, National Cancer Institute, Bethesda, MD 20892.
Bernstein
D C
DC
Shearer
G M
GM
D000328:Adult; D000956:Antigens, Viral / Q000276:immunology*; D002448:Cell Adhesion; D002469:Cell Separation; D003602:Cytotoxicity, Immunologic; D005434:Flow Cytometry; D006801:Humans; D007111:Immunity, Cellular; D009980:Influenza A virus / Q000276:immunology*; D007519:Isoantigens / Q000276:immunology*; D008213:Lymphocyte Activation / Q000528:radiation effects; D008212:Lymphocyte Depletion; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000528:radiation effects
D000956:Antigens, Viral; D007519:Isoantigens