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-1alpha and MIP-1beta. 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-1alpha and MIP-1beta increased with secondary immunizations, suggesting that memory CD8+ cells are involved. Treatment of CD8+ cell culture supernatant with antibodies to RANTES, MIP-1alpha and MIP-1beta neutralized the CD8-SF activity, indicating that blocking the CCR5 by these ligands played an important part in the CD8-SF activity elicited by TILN immunization. Indeed, blocking CCR5 with monoclonal antibodies inhibited SIV replications and MIP-1beta 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.
Wang
Y
Y
Department of Immunology, UMDS at Guy's Hospital, London, UK.
Tao
L
L
Mitchell
E
E
Bergmeier
L
L
Doyle
C
C
Lehner
T
T
D000818:Animals; D000906:Antibodies / Q000276:immunology; D065100:CCR5 Receptor Antagonists; D016827:CD8 Antigens / Q000276:immunology; D018925:Chemokines / Q000276:immunology / Q000378:metabolism*; D002634:Chemotaxis, Leukocyte; D005260:Female; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D007117:Immunization, Secondary; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000502:physiology; D008253:Macaca mulatta; D008297:Male; D008562:Membrane Glycoproteins; D019713:Receptors, CCR5 / Q000502:physiology*; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors / Q000502:physiology*; D018449:SAIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000276:immunology / Q000378:metabolism* / Q000502:physiology; D013491:Suppressor Factors, Immunologic / Q000378:metabolism; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology*; D014759:Viral Envelope Proteins; D014779:Virus Replication
D000906:Antibodies; D065100:CCR5 Receptor Antagonists; D016827:CD8 Antigens; D018925:Chemokines; D015699:HIV Envelope Protein gp120; D008562:Membrane Glycoproteins; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D018449:SAIDS Vaccines; D013491:Suppressor Factors, Immunologic; D014614:Vaccines, Synthetic; D014759:Viral Envelope Proteins; C069623:gp120 protein, Simian immunodeficiency virus