Effects of treatment with IL-2 receptor specific monoclonal antibody in mice. Inhibition of cytotoxic T cell responses but not of T help.
Contribution of IL-2R-bearing activated lymphocytes to antiviral host defense was investigated in C57BL/6 mice by treatment in vivo with IL-2R-specific mAb PC61. When treated on days 0 and 1 with respect to infection with either vaccinia virus, lymphocytic choriomeningitis (LCM) virus (LCMV) or vesicular stomatitis virus, 6-day immune mice had low numbers of CD8+ T cells that were reduced to about 10% of the values found for infected but otherwise untreated controls. In contrast, the number of CD4+ T cells was within normal ranges. Correspondingly, induction of strictly T help-dependent antiviral neutralizing IgG antibody titers remained unaffected by the mAb treatment, whereas generation of antiviral cytotoxic T cell activity was abrogated. Anti-IL-2R treatment of thymectomized mice 14 and 15 days after infection prevented generation of secondary antiviral cytotoxic T cells in restimulation cultures in vitro initiated 24 days later. Treatment with IL-2R-specific mAb was comparable to treatment with CD8-specific mAb in preventing mice to eliminate virus. Because of the involvement of antiviral cytotoxic T cells in disease manifestations, treatment with IL-2R-specific mAb protected mice from lethal LCM after intracerebral infection with LCMV and inhibited the footpad swelling reaction caused by local infection with the same virus.
Leist
T P
TP
Institute für Pathologie, Universitätsspital, Zürich, Switzerland.
Kohler
M
M
Eppler
M
M
Zinkernagel
R M
RM
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000145:classification; D000918:Antibody Specificity; D000920:Antibody-Dependent Cell Cytotoxicity; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology; D004487:Edema / Q000276:immunology; D005260:Female; D007117:Immunization, Secondary; D007074:Immunoglobulin G / Q000096:biosynthesis; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000145:classification; D008216:Lymphocytic Choriomeningitis / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D008819:Mice, Nude; D010641:Phenotype; D051381:Rats; D015375:Receptors, Interleukin-2 / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D014721:Vesicular stomatitis Indiana virus / Q000276:immunology
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D000956:Antigens, Viral; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D015375:Receptors, Interleukin-2