Allo-immunization elicits CCR5 antibodies, SDF-1 chemokines, and CD8-suppressor factors that inhibit transmission of R5 and X4 HIV-1 in women.
Studies in humans suggest that allo-immunization induces CC-chemokines, CD8-suppressor factors (SF) and anti-HIV immunity. Here we report that allo-immunization with unmatched leucocytes from partners of women with recurrent spontaneous abortion elicits specific antibodies to the CCR5 receptor. Such antibodies inhibit replication of M-tropic HIV-1 (R5) and MIP-1beta-mediated chemotaxis. These CCR5 antibodies were also found in the sera of multiparous women that were naturally immunized by semi-allogeneic fetal antigens. The specificity of these antibodies was demonstrated by adsorption with CCR5 transfected HEK-293 cells, a baculovirus CCR5 preparation and a peptide of the 2nd extra-cellular loop of CCR5. Allo-immunization also stimulated increased concentrations of the CXC chemokine, SDF-1alpha and CD8-SF that inhibit T-tropic HIV-1 (X4) replication. We suggest that allo- immunization may elicit (a) CC chemokines, CCR5 antibodies and CD8-SF that inhibit M-tropic HIV-1 infection and (b) the CXC chemokine SDF-1alpha and CD8-SF that inhibit T-tropic HIV-1 infection.
Peter Gorer Department of Immunobiology, Guy's, King's and St Thomas' Medical School, King's College London, UK.
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Wang
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Underwood
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Vaughan
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Harmer
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Doyle
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Lehner
D000026:Abortion, Habitual / Q000628:therapy; D000595:Amino Acid Sequence; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D002478:Cells, Cultured; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000096:biosynthesis*; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000276:immunology* / Q000635:transmission; D015497:HIV-1; D006801:Humans; D007114:Immunization; D007074:Immunoglobulin G / Q000097:blood; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control; D007518:Isoantibodies / Q000097:blood* / Q000276:immunology; D007519:Isoantigens / Q000276:immunology; D017708:Leukocyte Transfusion; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D008969:Molecular Sequence Data; D010298:Parity; D011247:Pregnancy; D019713:Receptors, CCR5 / Q000737:chemistry / Q000276:immunology*; D013491:Suppressor Factors, Immunologic / Q000096:biosynthesis / Q000494:pharmacology
C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D007074:Immunoglobulin G; D007518:Isoantibodies; D007519:Isoantigens; D019713:Receptors, CCR5; D013491:Suppressor Factors, Immunologic