Effects of anti-CD4 antibody: enhancement of lymph node PPD-memory T cell response.
In vitro incubations of CD4+ T cells with anti-CD4 monoclonal antibody (Mab) demonstrated saturation binding and inhibited both PPD-stimulated proliferation and delayed-type hypersensitivity (DTH) after passive transfer of these cells into naive rats. In comparison, in vivo administration of anti-CD4 Mab into rats, 2 weeks after CFA immunization (PPD priming), saturated CD4 molecules expressed on T lymphocytes and depleted significant percentages of CD4+ T cells from blood, spleen, and lymph nodes, yet failed to cause significant inhibition of PPD-stimulated DTH ear swelling. Only repeated in vivo administration of anti-CD4 Mabs during the CFA/PPD antigen priming caused significant decreases (36 +/- 5%) in PPD-stimulated DTH ear swelling. T cells isolated from the blood and spleen showed insignificant relative decreases in PPD-stimulated proliferation after anti-CD4 treatments. In contrast, PPD-stimulated proliferation of T cells isolated from the draining lymph nodes after anti-CD4 treatments showed dramatic increases in PPD reactivity. PPD stimulation of T cells isolated from the draining lymph nodes of anti-CD4 Mab-treated rats produced relative phenotypic changes in CD4 coexpressions with CD45RC (inverse memory), CD49d (inflammatory adhesion integrin VLA-4), and OX40 (CD4+ blast), representative of memory CD4+ T cell blasts with reduced capacity for endothelial infiltration. These data demonstrate that depletion of CD4+ T cells by anti-CD4 Mab injections, administered either during or after antigen priming, selectively enhanced memory responses in T lymphocytes in the draining lymph nodes.
Morrison
W J
WJ
Neuroimmunology Research Laboratory, Veterans Administration Medical Center, Portland, Oregon 97201, USA.
Kennedy
N J
NJ
Offner
H
H
Vandenbark
A A
AA
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology*; D015704:CD4 Antigens / Q000276:immunology*; D002460:Cell Line; D017637:Clonal Deletion / Q000276:immunology; D005434:Flow Cytometry; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007156:Immunologic Memory / Q000276:immunology*; D016130:Immunophenotyping; D008198:Lymph Nodes / Q000166:cytology; D008213:Lymphocyte Activation / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000276:immunology*; D014373:Tuberculin / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D014373:Tuberculin