CD8+ lymphocytes do not mediate protection against acute superinfection 20 days after vaccination with a live attenuated simian immunodeficiency virus.
In order to test the hypothesis that CD8+ cytotoxic T lymphocytes mediate protection against acute superinfection, we depleted >99% of CD8+ lymphocytes in live attenuated simian immunodeficiency virus macC8 (SIVmacC8) vaccinees from the onset of vaccination, maintained that depletion for 20 days, and then challenged with pathogenic, wild-type SIVmacJ5. Vaccinees received 5 mg per kg of humanized anti-CD8 monoclonal antibody (MAb) 1 h before inoculation, followed by the same dose again on days 3, 7, 10, 13, and 17. On day 13, peripheral CD8+ T lymphocytes were >99% depleted in three out of four anti-CD8 MAb-treated vaccinees. At this time attenuated SIVmacC8 viral RNA loads in anti-CD8 MAb-treated vaccinees were significantly higher than control vaccinees treated contemporaneously with nonspecific human immunoglobulin. Lymphoid tissue CD8+ T lymphocyte depletion was >99% in three out of four anti-CD8 MAb-treated vaccinees on the day of wild-type SIVmacJ5 challenge. All four control vaccinees and three out of four anti-CD8 MAb-treated vaccinees were protected against detectable superinfection with wild-type SIVmacJ5. Although superinfection with wild-type SIVmacJ5 was detected at postmortem in a single anti-CD8 MAb-treated vaccinee, this did not correlate with the degree of preceding CD8+ T lymphocyte depletion. Clearance of attenuated SIVmacC8 viremia coincided with recovery of normal CD8+ T lymphocyte counts between days 48 and 76. These results support the view that cytotoxic T lymphocytes are important for host-mediated control of SIV primary viremia but do not indicate a central role in protection against acute superinfection conferred by inoculation with live attenuated SIV.
Stebbings
Richard
R
Division of Immunology, NIBSC, Blanche Lane, South Mimms, Potters Bar, Hertfordshire EN6 3QG, United Kingdom. rstebbings@nibsc.ac.uk
Berry
Neil
N
Waldmann
Herman
H
Bird
Pru
P
Hale
Geoff
G
Stott
Jim
J
North
David
D
Hull
Robin
R
Hall
Joanna
J
Lines
Jenny
J
Brown
Stuart
S
D'Arcy
Nikki
N
Davis
Leanne
L
Elsley
William
W
Edwards
Cherry
C
Ferguson
Deborah
D
Allen
Jane
J
Almond
Neil
N
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D018655:Lymphocyte Count; D008212:Lymphocyte Depletion; D008252:Macaca fascicularis; D012367:RNA, Viral / Q000097:blood; D018449:SAIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000517:prevention & control / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D015163:Superinfection / Q000276:immunology* / Q000517:prevention & control; D013997:Time Factors; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000276:immunology*; D019562:Viral Load; D014766:Viremia
D000914:Antibodies, Viral; D012367:RNA, Viral; D018449:SAIDS Vaccines; D014613:Vaccines, Attenuated