Limited ability of humoral immune responses in control of viremia during infection with SIVsmmD215 strain.
We investigated the impact of rhesus macaque (RM) B-cell depletion before inoculation with the isolate SIVsmmD215. Seven RMs were treated every 3 weeks with 50 mg/kg of an anti-CD20 antibody (rituximab) starting 7 days before inoculation for 2 (n = 4) and 5 (n = 3) months. Four control animals received no antibody. Three animals were completely depleted of CD20(+) B cells, but 4 were only partially depleted of CD20 cells in the LNs and intestine. The decrease in antibody production was consistent with the efficacy of tissue CD20 depletion. Seroconversion and neutralizing antibody production was significantly delayed in animals showing complete tissue CD20 depletion and remained at low titers in all CD20-depleted RMs. Surprisingly, there was no significant difference in acute or chronic viral loads between CD20-depleted and control animal groups. There was a tendency for lower viral set points in CD20-depleted animals. At 6 weeks after inoculation, cellular immune responses were significantly stronger in CD20-depleted animals than in controls. There was no significant difference in survival between CD20-depleted and control animals. Our data suggest that a deficiency of Ab responses did not markedly affect viral replication or disease progression and that they may be compensated by more robust cellular responses.
Gaufin
Thaidra
T
Division of Microbiology, Tulane National Primate Research Center, Covington, LA 70433, USA.
Gautam
Rajeev
R
Kasheta
Melissa
M
Ribeiro
Ruy
R
Ribka
Erin
E
Barnes
Mary
M
Pattison
Melissa
M
Tatum
Coty
C
MacFarland
Jeanne
J
Montefiori
David
D
Kaur
Amitinder
A
Pandrea
Ivona
I
Apetrei
Cristian
C
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D058846:Antibodies, Monoclonal, Murine-Derived; D000914:Antibodies, Viral / Q000276:immunology*; D000917:Antibody Formation / Q000502:physiology; D018951:Antigens, CD20 / Q000276:immunology; D001402:B-Lymphocytes / Q000502:physiology; D005434:Flow Cytometry; D007111:Immunity, Cellular; D007124:Immunoenzyme Techniques; D007155:Immunologic Factors / Q000494:pharmacology; D007422:Intestines / Q000276:immunology / Q000821:virology; D008213:Lymphocyte Activation / Q000187:drug effects; D008212:Lymphocyte Depletion; D008253:Macaca mulatta; D008297:Male; D000069283:Rituximab; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000472:pathogenicity*; D013601:T-Lymphocytes / Q000276:immunology; D019562:Viral Load; D014766:Viremia / Q000517:prevention & control*; D014779:Virus Replication / Q000187:drug effects
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000914:Antibodies, Viral; D018951:Antigens, CD20; D007155:Immunologic Factors; D000069283:Rituximab