title: In vitro naïve T cell proliferation failure predicts poor post-immunization responses to neoantigen, but not recall antigens, in HIV-infection.
abstract: 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.
authors.affiliation: Case Western Reserve University Center for AIDS Research, Cleveland, OH 44106-5083, USA. rodriguez.benigno@clevelandactu.org
authors.forename: Benigno
authors.initials: B
authors.lastname: Rodriguez
authors.forename: Hernan
authors.initials: H
authors.lastname: Valdez
authors.forename: Christoph G
authors.initials: CG
authors.lastname: Lange
authors.forename: Robert
authors.initials: R
authors.lastname: Asaad
authors.forename: Kathy
authors.initials: K
authors.lastname: Medvik
authors.forename: Scott F
authors.initials: SF
authors.lastname: Sieg
mesh_terms: 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
chemical_list: D000941:Antigens; D013745:Tetanus Toxoid; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin
references.citation: N Engl J Med. 1998 Mar 26;338(13):853-60
references.pmid: 9516219
references.citation: Immunol Cell Biol. 2004 Feb;82(1):38-46
references.pmid: 14984593
references.citation: J Clin Invest. 2001 Sep;108(5):757-64
references.pmid: 11544282
references.citation: AIDS. 2000 Jan 7;14(1):11-21
references.pmid: 10714563
references.citation: AIDS. 2003 Sep 26;17(14):2015-23
references.pmid: 14502004
references.citation: J Infect Dis. 2002 May 15;185(10):1401-16
references.pmid: 11992274
references.citation: Proc Natl Acad Sci U S A. 2003 Dec 9;100(25):15011-6
references.pmid: 14645713
references.citation: Proc Natl Acad Sci U S A. 2001 Nov 20;98(24):13878-83
references.pmid: 11717444
references.citation: AIDS. 2008 Oct 18;22(16):2143-53
references.pmid: 18832878
references.citation: AIDS. 1998 Oct 1;12(14):1745-51
references.pmid: 9792374
references.citation: J Immunol. 2003 Nov 15;171(10):5208-14
references.pmid: 14607921
references.citation: J Exp Med. 2004 Oct 4;200(7):587-99
references.pmid: 15508184
references.citation: J Virol. 2004 Nov;78(22):12638-46
references.pmid: 15507650
references.citation: Curr HIV Res. 2004 Jan;2(1):11-21
references.pmid: 15053337
references.citation: J Antimicrob Chemother. 2003 Jan;51(1):1-4
references.pmid: 12493779
references.citation: J Infect Dis. 2003 Jan 15;187(2):320-5
references.pmid: 12552459
references.citation: AIDS. 2004 Jan 2;18(1):89-97
references.pmid: 15090834
references.citation: Lancet. 2007 Jul 7;370(9581):59-67
references.pmid: 17617273
references.citation: J Infect Dis. 2003 Dec 15;188(12):1794-803
references.pmid: 14673757
references.citation: J Immunol. 2003 Jun 15;170(12):5965-72
references.pmid: 12794123
references.citation: J Immunol. 2004 Apr 15;172(8):4907-16
references.pmid: 15067070
references.citation: Blood. 2003 Jun 1;101(11):4505-11
references.pmid: 12576311
references.citation: JAMA. 2006 Sep 27;296(12):1498-506
references.pmid: 17003398
references.citation: N Engl J Med. 1981 Dec 10;305(24):1425-31
references.pmid: 6272109
references.citation: J Acquir Immune Defic Syndr. 2007 Sep 1;46(1):72-7
references.pmid: 17621240
references.citation: J Infect Dis. 2000 Sep;182(3):792-8
references.pmid: 10950773
references.citation: Nat Rev Immunol. 2005 Nov;5(11):835-43
references.pmid: 16239902
references.citation: J Clin Invest. 1989 Dec;84(6):1892-9
references.pmid: 2574188
references.citation: Nat Immunol. 2002 Nov;3(11):1061-8
references.pmid: 12368910
references.citation: Curr Mol Med. 2006 Sep;6(6):621-9
references.pmid: 17022732
references.citation: Clin Exp Immunol. 1996 Sep;105(3):409-15
references.pmid: 8809127
references.citation: Ann Intern Med. 2007 Jan 16;146(2):87-95
references.pmid: 17227932
references.citation: Nat Med. 1999 May;5(5):518-25
references.pmid: 10229228
references.citation: J Allergy Clin Immunol. 1999 Feb;103(2 Pt 1):192-9
references.pmid: 9949307
references.citation: FASEB J. 2006 Nov;20(13):2198-208
references.pmid: 17077296
references.citation: AIDS. 2007 Sep 12;21(14):1957-63
references.pmid: 17721103
references.citation: J Infect Dis. 1995 Mar;171(3):531-6
references.pmid: 7876598
references.citation: J Immunol. 2004 Aug 1;173(3):2184-9
references.pmid: 15265956
references.citation: J Clin Immunol. 1990 Mar;10(2):121-7
references.pmid: 2140115
references.citation: Curr HIV Res. 2004 Jan;2(1):23-37
references.pmid: 15053338
references.citation: AIDS. 2001 Feb;15 Suppl 2:S11-5
references.pmid: 11424971
references.citation: Blood. 2004 Mar 15;103(6):2180-6
references.pmid: 14604962
references.citation: Clin Immunol. 2002 Feb;102(2):154-61
references.pmid: 11846457