Immunosuppression by anti-CD4 treatment in vivo. Cellular and humoral responses to alloantigens.
Antibody-mediated elimination of CD4+ lymphocytes in vivo has been successfully used to suppress the humoral response to foreign antigens and to induce long-term tolerance. However, secondary humoral responses, as well as secondary cytolytic responses specific for viral antigens, could not be prevented, providing evidence for functional heterogeneity within the helper cell compartment. Data presented here support the notion that helper cell requirements for cellular responses to alloantigens are unique and do not involve CD4+ T lymphocytes. While the administration of anti-CD4 mcAb failed to suppress allospecific CTL responses, the formation of alloantibodies was initially inhibited in parallel to the deficiency in CD4+ helper cells. After regeneration of CD4+ T cells, the animals regained the ability to produce specific IgG alloantibodies. The dichotomy of helper pathways in humoral and cellular alloreactive responses challenges the concept of a single CD4+ helper cell population. Insights into the functional heterogeneity of helper cells for primary, secondary, and allospecific responses might open new avenues for selective manipulation of helper subpopulations.
Weyand
C M
CM
Department of Medicine, Heidelberg University Medical School, Federal Republic of Germany.
Goronzy
J
J
Swarztrauber
K
K
Fathman
C G
CG
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D000920:Antibody-Dependent Cell Cytotoxicity; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D000961:Antilymphocyte Serum / Q000096:biosynthesis*; D000939:Epitopes / Q000276:immunology; D007111:Immunity, Cellular; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D007519:Isoantigens / Q000276:immunology*; D051379:Mice; D008805:Mice, Inbred A; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000378:metabolism
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D000961:Antilymphocyte Serum; D000939:Epitopes; D007166:Immunosuppressive Agents; D007519:Isoantigens