In vitro naïve T cell proliferation failure predicts poor post-immunization responses to neoantigen, but not recall antigens, in HIV-infection.
Immune reconstitution after HAART is incomplete, but no widely accepted method to quantify subclinical immune deficiency is available. We immunized 9 HIV-negative subjects and 29 HIV-infected patients with CD4>/=450 cells/microL and undetectable HIV RNA levels with 2 doses of diphtheria/tetanus toxoid (TT) and KLH, a presumed neoantigen. We quantified the response by lymphoproliferative assay, delayed-type hypersensitivity (DTH), and antibody titers up to 59days after enrollment. We assessed T cell proliferative capacity using anti-Vbeta3 and anti-Vbeta5 antibody stimulation, which we herein show induced predominant proliferation of naïve T cells. Subjects with detectable responses to KLH tended to exhibit greater proliferative responses to anti-Vbeta3/Vbeta5 stimulation; no such pattern was seen with response to TT. Several measures of in vitro T cell proliferative capacity correlated significantly with DTH and antibody responses to KLH, but not with TT responses; this association was independent of naïve T cell numbers. Our results indicate that naïve T cell proliferation predicts response to neo-, but not recall antigens, and suggest that it may be a meaningful reflection of in vivo immune competence in HIV-infected persons.
Rodriguez
Benigno
B
Case Western Reserve University Center for AIDS Research, Cleveland, OH 44106-5083, USA. rodriguez.benigno@clevelandactu.org
Valdez
Hernan
H
Lange
Christoph G
CG
Asaad
Robert
R
Medvik
Kathy
K
Sieg
Scott F
SF
D000328:Adult; D000917:Antibody Formation; D000941:Antigens / Q000008:administration & dosage; D023241:Antiretroviral Therapy, Highly Active; D016022:Case-Control Studies; D049109:Cell Proliferation; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000628:therapy; D006433:Hemocyanins / Q000008:administration & dosage; D006801:Humans; D006968:Hypersensitivity, Delayed; D007114:Immunization; D007115:Immunization Schedule; D007121:Immunocompetence; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D013745:Tetanus Toxoid / Q000008:administration & dosage
D000941:Antigens; D013745:Tetanus Toxoid; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin
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