Mucosal alloimmunization elicits T-cell proliferation, CC chemokines, CCR5 antibodies and inhibition of simian immunodeficiency virus infectivity.
The hypothesis was tested that mucosal stimulation with unmatched mononuclear cells would induce systemic alloimmune responses. Rectal or vaginal mucosal administration of 10(4)-10(7) unmatched mononuclear cells induced significant dose-dependent T-cell proliferation stimulated by the allogeneic cells in rhesus macaques. This was associated with a significant upregulation of CD8(+) T-cell-derived suppressor factor, as well as the CC chemokines CCL3, CCL4 and CCL5. In addition, there was a dose-dependent increase in antibodies to CCR5. These responses were associated with decreased in vitro simian immunodeficiency virus (SIV) infectivity of CD4(+) T cells. A further investigation of SIV infectivity of CD4(+) T cells separated from multiparous macaques also showed significant inhibition compared with male macaques. It is suggested that vaginal or rectal exposure to allogeneic stimulation by a partner's HLA antigens in seminal fluid, as occurs during sexual intercourse, or immunization by semi-allogeneic fetuses in multiparous females may elicit protection against SIV or human immunodeficiency virus infection.
Bergmeier
Lesley A
LA
Mucosal Immunology Unit, Guy's, King's and St Thomas' Hospital Medical and Dental Schools, King's College London, London SE1 9RT, UK.
Babaahmady
Kaboutar
K
Mucosal Immunology Unit, Guy's, King's and St Thomas' Hospital Medical and Dental Schools, King's College London, London SE1 9RT, UK.
Wang
Yufei
Y
Mucosal Immunology Unit, Guy's, King's and St Thomas' Hospital Medical and Dental Schools, King's College London, London SE1 9RT, UK.
Lehner
Thomas
T
Mucosal Immunology Unit, Guy's, King's and St Thomas' Hospital Medical and Dental Schools, King's College London, London SE1 9RT, UK.
D000282:Administration, Intravaginal; D000285:Administration, Rectal; D000818:Animals; D000906:Antibodies / Q000097:blood*; D000918:Antibody Specificity; D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D019742:Chemokines, CC / Q000096:biosynthesis*; D005260:Female; D007114:Immunization; D007519:Isoantigens / Q000008:administration & dosage* / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008213:Lymphocyte Activation; D008253:Macaca mulatta; D008297:Male; D019713:Receptors, CCR5 / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000517:prevention & control; D015302:Simian Immunodeficiency Virus / Q000472:pathogenicity / Q000502:physiology*
D000906:Antibodies; D019742:Chemokines, CC; D007519:Isoantigens; D019713:Receptors, CCR5