title: Mechanisms of protection induced by attenuated simian immunodeficiency virus. II. Lymphocyte depletion does not abrogate protection.
abstract: To determine the role that cellular immune responses play in the protection conferred by vaccination with attenuated SIVmac32H (pC8), we have attempted to deplete macaques of their CD8+ cells prior to challenge with wild-type SIVmac32H (pJ5). In two of four pC8-infected macaques, N109 and N112, a transient partial depletion of CD8+ cells by antibody treatment was achieved. On the day of challenge peripheral CD2+CD4-CD8+ cell counts were reduced by 92 and 95%, respectively, in animals N109 and N112 and their lymph nodes revealed a 46 and 58% reduction, respectively, in CD2+CD4-CD8+ cells. Two other pC8-immunized macaques, N110 and N111, treated in the same way, did not show significant depletion of CD8+ cells. None of these four pC8-immunized animals became infected when challenged with 50 MID50 of pJ5. Treatment of a further four pC8-infected and protected macaques and two naive control animals with Campath-1H antibody successfully depleted peripheral CD3+ cell counts by >99% in all treated animals. Campath-1H depletion resulted in enhanced, longer lasting lymphoid depletion. Yet subsequent challenge with 20 MID50 of pJ5 still failed to infect the pC8-immunized animals. All eight of the naive controls, including two Campath-1H-treated animals, became infected following challenge. In summary, partial depletion of circulating CD8+ cells or total lymphocytes prior to challenge failed to abrogate the protection conferred by vaccination with pC8.
authors.affiliation: Division of Immunobiology, National Institute for Biological Standards and Control, South Mimms, Potters Bar, Herts, UK.
authors.forename: R
authors.initials: R
authors.lastname: Stebbings
authors.forename: J
authors.initials: J
authors.lastname: Stott
authors.forename: N
authors.initials: N
authors.lastname: Almond
authors.forename: R
authors.initials: R
authors.lastname: Hull
authors.forename: J
authors.initials: J
authors.lastname: Lines
authors.forename: P
authors.initials: P
authors.lastname: Silvera
authors.forename: R
authors.initials: R
authors.lastname: Sangster
authors.forename: T
authors.initials: T
authors.lastname: Corcoran
authors.forename: J
authors.initials: J
authors.lastname: Rose
authors.forename: S
authors.initials: S
authors.lastname: Cobbold
authors.forename: F
authors.initials: F
authors.lastname: Gotch
authors.forename: A
authors.initials: A
authors.lastname: McMichael
authors.forename: B
authors.initials: B
authors.lastname: Walker
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D005260:Female; D005434:Flow Cytometry; D007111:Immunity, Cellular; D018655:Lymphocyte Count; D008212:Lymphocyte Depletion; D008252:Macaca fascicularis; D008297:Male; D009500:Neutralization Tests; D018449:SAIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000517:prevention & control*; D015302:Simian Immunodeficiency Virus / Q000276:immunology* / Q000302:isolation & purification; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D018449:SAIDS Vaccines; D014613:Vaccines, Attenuated