The effect of immunization on chemokines and CCR5 and CXCR4 coreceptor functions in SIV binding and chemotaxis

The replication of simian immunodeficiency virus (SIV) in acutely infected CD4(+) cells can be inhibited in vitro by CD8-suppressor factors (SF) and b eta-chemokines induced by immunization of macaques with SIV gp120 and p27 i n Alum. A comparison between intradermal, naso-rectal-i.m. and targeted ili ac lymph node (TILN) routes showed that immunization by the TILN route elic ited the most significant increase in CD8-SF and the beta-chemokines RANTES , MIP-1 alpha and MIP-1 beta. Increased CD8-SF and beta-chemokines were ind uced not only in PBMC but also in iliac lymph nodes and spleen of the TILN immunized macaques. Furthermore, CD8-SF and the concentrations of RANTES, M IP-1 alpha and MIP-1 beta increased with secondary immunizations, suggestin g that memory CD8(+) cells are involved. Treatment of CD8(+) cell culture s upernatant with antibodies to RANTES, MIP-1 alpha and MIP-1 beta neutralize d the CD8-SF activity, indicating that blocking the CCR5 by these ligands p layed an important part in the CDS-SF activity elicited by TILN immunizatio n. Indeed, blocking CCR5 with monoclonal antibodies inhibited SIV replicati ons and MIP-1 beta mediated chemotaxis. In contrast, SDF-1 or MAb to CXCR4 failed to suppress SIV replication. However, SDF-1 was able to induce simia n PBMC chemotaxis and MAb to CXCR4 inhibited SDF-1 mediated chemotaxis. The se results suggest that immunization in macaques induces CD8-SF and beta-ch emokines which may prevent SIV infection by blocking the CCR5 coreceptors b oth in circulating cells and in the rectal and genital draining lymph node cells. (C) 1999 Elsevier Science Ltd. All rights reserved.