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 printing), 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), CD49^d (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.