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 beta-chemokines induced by immunization of macaques with SIV gp120 and p27 in Alum. A comparison between intradermal, naso-rectal-i.m. and targeted iliac lymph node (TILN) routes showed that immunization by the TILN route elicited 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 induced 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, MIP-1 alpha and MIP-1 beta increased with secondary immunizations, suggesting that memory CD8(+) cells are involved. Treatment of CD8(+) cell culture supernatant with antibodies to RANTES, MIP-1 alpha and MIP-1 beta neutralized the CD8-SF activity, indicating that blocking the CCR5 by these ligands played an important part in the CDS-SF activity elicited by TILN immunization. Indeed, blocking CCR5 with monoclonal antibodies inhibited SIV replications 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 simian PBMC chemotaxis and MAb to CXCR4 inhibited SDF-1 mediated chemotaxis. These results suggest that immunization in macaques induces CD8-SF and beta-chemokines which may prevent SIV infection by blocking the CCR5 coreceptors both in circulating cells and in the rectal and genital draining lymph node cells. (C) 1999 Elsevier Science Ltd. All rights reserved.