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Oral Presentations - Federation of Clinical Immunology Societies

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S32 Abstracts<br />

São Paulo, São Paulo, Brazil, Léia C. Rodrigues Silva, PhD<br />

Student, Laboratory <strong>of</strong> Dermatology and<br />

Immunodeficiencies, Medical School <strong>of</strong> the University <strong>of</strong><br />

São Paulo, São Paulo, Brazil, Guilherme G. Silveira,<br />

Student, Laboratory <strong>of</strong> Dermatology and<br />

Immunodeficiencies, Medical School <strong>of</strong> the University <strong>of</strong><br />

São Paulo, São Paulo, Brazil, Maury M. Tanji, Laboratory <strong>of</strong><br />

Dermatology and Immunodeficiencies, Medical School <strong>of</strong><br />

the University <strong>of</strong> São Paulo, São Paulo, Brazil, Denise<br />

Schout, Epidemiology Service, Hospital das Clínicas,<br />

Medical School <strong>of</strong> the University <strong>of</strong> São Paulo, São Paulo,<br />

Brazil, Alberto J.S. Duarte, Pr<strong>of</strong>essor, Laboratory <strong>of</strong><br />

Dermatology and Immunodeficiencies, Medical School <strong>of</strong><br />

the University <strong>of</strong> São Paulo, São Paulo, Brazil<br />

Background: The degree Mycobacterium tuberculosis (Mtb)<br />

immune reconstitution provided by long-term (N4 years)<br />

successful HAART and whether a past tuberculosis (TB) history<br />

influences this reconstitution are not known. Methods: We<br />

compared the lymphocyte proliferative response (LPR) and IFNã<br />

secretion to phytohemagglutinin (PHA) and Mtb antigens<br />

(ESAT6, Ag85B and whole Mtb lysate [SMtb]) <strong>of</strong> immunereconstituted<br />

(CD4 N500 cells/ìl) HIV+ patients with a past history <strong>of</strong><br />

cured TB (HIV+ CTB group) or latent infection as presumed by<br />

positive purified protein derivative skin test (PPD+) (HIV+ PPD+<br />

group) with HIV− controls either cured from TB (CTB group) or<br />

PPD reactors (PPD+ group). The databank on TB incidence<br />

among HIV+ and HIV− patients at our services during 1999–2005<br />

was also analyzed. Results: Most HIV+ patients presented normal<br />

PHA responses. However, Mtb immune reconstitution was<br />

incomplete, especially to ESAT6 and Ag85B. SMtb reactivity<br />

was fully restored in the HIV+ CTB group, while in HIV+ PPD+<br />

patients it remained lower than in PPD+ controls. Comparison<br />

between the two HIV groups also suggested better immune<br />

reconstitution in HIV+ CTB patients. Databank analysis revealed<br />

that some HIV+ patients with N360 CD4 cells/ìl still developed<br />

TB, but not those with previous TB history. Conclusions: Mtb<br />

immune reconstitution is incomplete in HIV+ CTB and HIV+ PPD<br />

+ patients even after highly successful HAART. However,<br />

reactivity to whole mycobacteria antigens is restored,<br />

especially in HIV+ CTB patients, possibly due to survival <strong>of</strong><br />

higher numbers <strong>of</strong> mycobacteria-specific T cell clones throughout<br />

immunosuppression, probably allowing sufficient protection<br />

against new Mtb challenges.<br />

doi:10.1016/j.clim.2007.03.266<br />

F.53 Human CD8+ Cytotoxic T Lymphocyte Epitopes<br />

Identified from Herpes Simplex Virus Type 1<br />

Glycoprotein D<br />

Aziz Alami Chentoufi, Assistant Specialist, Cellular and<br />

Molecular <strong>Immunology</strong> Laboratory, The Eye Institute,<br />

University <strong>of</strong> California, Irvine, Orange, CA, Xiuli Zhang,<br />

Postdoctoral Fellow, Cellular and Molecular <strong>Immunology</strong><br />

Laboratory, The Eye Institute, University <strong>of</strong> California,<br />

Irvine, Orange, CA, Kasper Lamberth, Researcher, Institute<br />

<strong>of</strong> Medical Microbiology and <strong>Immunology</strong> (IMMI), University<br />

<strong>of</strong> Copenhagen, 2200 Copenhagen, Denmark, Xiaoming Zhu,<br />

Research Associate, Cellular and Molecular <strong>Immunology</strong><br />

Laboratory, The Eye Institute, University <strong>of</strong> California,<br />

Irvine, Orange, CA, Gargi Dasgupta, Research Associate,<br />

Cellular and Molecular <strong>Immunology</strong> Laboratory, The Eye<br />

Institute, University <strong>of</strong> California, Irvine, orange, CA,<br />

Michele Wu, Student, Cellular and Molecular <strong>Immunology</strong><br />

Laboratory, The Eye Institute, University <strong>of</strong> California,<br />

Irvine, Orange, CA, Alex Nguyen, Bio-199 Student, Cellular<br />

and Molecular <strong>Immunology</strong> Laboratory, The Eye Institute,<br />

University <strong>of</strong> California, Irvine, Orange, CA, Ilham Bettahi,<br />

Postdoctoral Fellow, Cellular and Molecular <strong>Immunology</strong><br />

Laboratory, The Eye Institute, University <strong>of</strong> California,<br />

Irvine, Orange, CA, Søren Buus, Pr<strong>of</strong>essor, Institute <strong>of</strong><br />

Medical Microbiology and <strong>Immunology</strong> (IMMI), University <strong>of</strong><br />

Copenhagen, 2200 Copenhagen, Denmark, Lbachir<br />

BenMohamed, Assistant Pr<strong>of</strong>essor, Cellular and Molecular<br />

<strong>Immunology</strong> Laboratory, The Eye Institute, University <strong>of</strong><br />

California, Irvine, Orange, CA<br />

Cytolystic T cells (CTLs) play a major role in herpes simplex<br />

virus type 1 and type 2 (HSV-1 and HSV-2) infections and<br />

diseases. Among some eleven HSV-1 and HSV-2 coat glycoproteins,<br />

glycoprotein D (gD) induces immunodominant T cells and<br />

is a leading vaccine candidate antigen. However, little is known<br />

about human CD8+ T cell epitopes <strong>of</strong> gD. Based on predictive<br />

computational algorithms and peptide binding affinity to HLA-<br />

A*0201 molecules, we have identified ten regions within the<br />

HSV-1 gD, each 9 to 10 amino acids in length, exhibiting high<br />

affinity CD8+ Tcell epitope(s). T2 cell stabilization assay showed<br />

peptide gD53-61, gD70-78 and gD278-286 significantly, and in<br />

dose-dependent manner, upregulates HLA-A*0201 molecules<br />

expression.Toobtainanobjectiveenumeration<strong>of</strong>CD8+Tcells<br />

induced by each gD peptide epitope, we employed the HLA-<br />

A*0201 tetramer staining procedure. A relatively high percentages<br />

<strong>of</strong> CD8+ Tcells positive for gD-18-10, gD53-61, gD70-78 and<br />

gD278-286/HLA-A*0201 tetramers were detected in PBMC from<br />

HLA-A*0201 seropositive patients, either directly ex vivo or<br />

following a single in vitro stimulation. Accordingly, strong HLA-<br />

A*0201-restricted CD8+ CTLs, assessed by INF-γ-ELISPOT and<br />

CD107a/b cytotoxic assays, were mapped to gD53-61, gD70-78<br />

and gD278-286 peptides. However, only gD53-61 and gD278-286<br />

peptides were able to generate CD8+ T cells that recognize<br />

infected target cells. Collectively, these findings suggest that<br />

high-affinity HLA-A*0201-binding gD53-61 and gD278-286 epitopes<br />

are naturally processed and are recognized by HSVspecific<br />

CD8+ CTLs in the infected human population, providing<br />

important information for the development <strong>of</strong> subunit vaccine<br />

strategies against herpes.<br />

doi:10.1016/j.clim.2007.03.267<br />

F.55 Protection Against SEB-Induced Toxic Shock by<br />

Anti-TCR Vb8 Antibody<br />

Manisha Singh, Postdoctoral Associate, Baylor College <strong>of</strong><br />

Medicine, <strong>Immunology</strong> Department, Houston, TX<br />

Intraperitoneal injection <strong>of</strong> the bacterial superantigen,<br />

Staphylococcus enterotoxin B (SEB) in HLA-DR3 transgenic<br />

mice leads to toxic shock and death within 72 h. In vivo,<br />

this is characterized by a marked expansion <strong>of</strong> splenic TCR<br />

Vb8+ CD4 and CD8 T cells compared to PBS treated mice. It

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