Effects of CKS-17, a synthetic retroviral envelope peptide, on cell-mediated immunity in vivo: immunosuppression, immunogenicity, and relation to immunosuppressive tumor products.
CKS-17 is a heptadecapeptide corresponding to a region highly conserved in retroviral transmembrane proteins such as p15E. Because a relationship had previously been determined between p15E and immunosuppressive tumor cell products, we examined the effect of CKS-17, control peptides and conjugates thereof on the expression of cell-mediated immunity (delayed-type hypersensitivity, DTH) in mice. Conjugates of CKS-17 inhibited DTH reactions to sheep erythrocytes in the feet of mice. The degree of inhibition was dose-dependent. Unconjugated CKS-17 had almost no effect, and control peptide conjugates had no inhibitory effect. Immunization of mice with CKS-17 conjugates, but not with control conjugates, rendered them resistant to the depression of DTH reactions, not only by CKS-17 conjugates, but also by products of cultured tumor cells. CKS-17 conjugates, but not control conjugates, also depressed the cellular inflammatory reactions induced in mouse footpads by concanavalin A (ConA) and immunized mice against the depression of ConA reactions by products of cultured tumor cells. Injections of globulin from sera of mice immunized with CKS-17 conjugates conferred upon normal recipients resistance to the depression of footpad reactions to ConA by products of cultured tumor cells. Globulin from sera of normal mice or control immunized mice did not confer such resistance. Thus conjugates of a synthetic peptide not only mimic the immunosuppressive effects of tumor products in vivo, but can also immunize mice against those effects.
Nelson
M
M
Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney, Australia.
Nelson
D S
DS
Cianciolo
G J
GJ
Snyderman
R
R
D000818:Animals; D003208:Concanavalin A / Q000494:pharmacology; D006968:Hypersensitivity, Delayed; D007111:Immunity, Cellular / Q000187:drug effects*; D007114:Immunization; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000276:immunology*; D010455:Peptides / Q000276:immunology / Q000494:pharmacology*; D015682:Retroviridae Proteins, Oncogenic / Q000494:pharmacology*
D007166:Immunosuppressive Agents; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D015682:Retroviridae Proteins, Oncogenic; D003208:Concanavalin A; C053692:CKS 17