Abstract Book Vol. 2 [International Conference on AIDS (14th: 2002: Barcelona, Spain)]

374 Abstracts ThPeA7162-ThPeA7166

XIV International AIDS Conference

ThPeA7162 ICD8+ T cells that express CD4 on their surface
produce elevated levels of IL-4, are detected in vivo,
and can be infected by T-tropic HIV: Relevance to
HIV pathogenesis in the CD8+ T cell compartment
Y.B. Sullivan, A. Landay, L. AI-Harthi. Rush Medical College, Chicago, United
States
Background: CD8+ T cells can up-regulate CD4 on their cell surface, to generate
CD4CD8 phenotype. We previously demonstrated that CD4CD8 are an activated
phenotype of CD8+ T cells, as determined by elevated levels of activation (CD95,
CD25, CD38, CD69, and CD45RO) and functional (CD28) markers. In this study,
we evaluated intracellular cytokine profile of these cells, impact of stage of HIV
disease on generating this phenotype, HIV infection of these cells, and in vivo
evidence for the existence of CD4CD8 T cells in HIV+ patients.
Methods: CD4 upregulation on CD8 T cells was generated by both superantigen
(SEB) and soluble anti-CD3/CD28 co-stimulation. Expression of CD4CD8 cells
was monitored by standard flow cytometry. Intracellular cytokine expression was
evaluated by intracellular staining of type 1 and type 2 cytokines in a flow-based
assay. HIV infection of CD4CD8 T cells was evaluated by intracellular p24 expression.
Results: While CD4CD8 T cells do not produce significant intracellular levels of
INFy, IL-2, or IL-10, they express elevated levels of intracellular IL-4 in comparison to CD8+CD4- and CD4+ T cells. CD4CD8 T cells express both CXCR4 and
CCR5 but in response to either soluble anti-CD3/CD28 or SEB stimulation, they
were susceptible to T-tropic and not M-tropic HIV infection. A soluble factor believed to be P-chemokine is responsible for the inhibition of M-tropic HIV infection
in CD4CD8 T cells. CD8+ T cells from HIV+ patients at various stages of HIV
disease were capable of up-regulating CD4 on CD8+ T cells. We also provide
evidence of the presence of CD4CD8 T cells in HIV+ patients.
Conclusions: Our data collectively indicate that CD4CD8 T cells constitute an
activated phenotype of CD8+ T cells and that they may play a critical role in normal T cell immunology and in HIV pathogenesis.
Presenting author: Lena AI-Harthi, 1653 West Harrison St. Rm. 1577JSC,
Chicago, IL 60612, United States, Tel.: [phone], Fax: [phone],
E-mail: lalharth @rush.edu
ThPeA7163 Evaluation of cervical immunity in HIV-1 and HPV
infected women
A.F Nicol', A.T.G. Fernandes', B.G.J. Grinsztejn', F. Russomano2,
0. Martinez-Maza3, J.R. Lapa e Silva4, M.G. Bonecini-Almeidal. 'Fiocruz, Rua
Paranhos 213, casa 03 Ramos, Rio de Janeiro, Brazil; 2IFF/Fiocruz, Rio de
Janeiro, Brazil; 3 UCLA, Los Angeles, United States; 4HUCFF, Rio de Janeiro-RJ,
Brazil
Background: The women have assumed an important role in the epidemic of
HIV-1 infection, however little is known about the immune system of the female
genital tract. The HIV immunosuppression exacerbates co-existing HPV infection, the development of cervical cancer. Objective: In order to characterize the
cervical immune response, we analyzed inflammatory cells and cytokines profile in HIV/HPV co-infected women. Materials and Methods: 32 cervical biopsies
obtained from (16) HIV positive and (16) negative women were snap frozen in
liquid nitrogen. Tissue sections were underwent immunoperoxidase staining using antibodies directed to CD68, CD4, CD8, and IL-6, IL-8, TNF-alfa, IL-4, IL-10,
IL-12 and IFN-gamma intracellular cytokines. Low and high risk HPV type were
performed in all samples.
Results: In the HIV/HPV (12 in 16 patients) infected women the HIV viral load varied from 80 to 260.000 copies, peripheral TCD4+ varied from 16 to 685 mm3. High
risk HPV type of malignant transformation was detected in 80% of these patients.
Cervical biopsies from HIV/HPV infected women showed significantly decreased
expression of IL-6 (0.4~0.5); IFN-gamma (0.6~0.6) and TNF-alfa (1.63~0.6)
compared to HPV infected patients (6.5~2.0, p=0.02; 8.0~2,5 p=0.02; 12.1~3.1
p=0.01) respectively Great number of mature macrophage and T lymphocytes
(CD4 and CD8) was seen in both studied groups, although a marked number of
T CD8+ was observed in co-infected patients (p=0.08).
Conclusions: The majority of co-infected patients harbor high risk HPV type and
may have an increase risk to develop cervical cancer. HPV infection trigger the
migration of HIV-1 reservoir cells contributing to HIV replication in HIV/HPV coinfected women. However, we demonstrated low expression of cytokines that enhance HIV replication. Others mechanisms could be probably involved and should
be addressed on cervical lesion.
Presenting author: Alcina Nicol, Rua Paranhos 213, casa 03 Ramos, Rio de
Janeiro, Brazil, Tel.: [phone], Fax: [phone], E-mail: nicol
@cpqhec.fiocruz.br
ThPeA7164 Analysis of HIV- and CMV-specific memory CD4 T
cell responses during primary and chronic

infections
A. Harari', G.P. Rizzardil, K. Ellefsen', D. Ciuffredal, M. Khonkarly',
L. Kaiser2, L. Perrin2, G. Pantaleol. 'Lab of AIDS Immunopathogenesis,
Laboratory of AIDS Immunopathogenesis, Hopital Beaumont-CHUV, 29 Av
Beaumont, 1011 Lausanne, Switzerland; 2Lab of Virology, Geneve, Switzerland
Background: HIV-1-specific CD4 helper responses are thought to be lost very

early during HIV infection and recent studies have demonstrated that the preservation of these responses may be critical for the control of HIV-1 replication. However, even in the absence of lymphoproliferative responses, HIV-1-specific IFNg
secreting cells CD4 T cells, were detected in patients with chronic infection
Methods: CD4 T cell-specific antiviral responses to HIV-1 and to cytomrnegalovirus
(CMV) and the distribution of HIV-1 viral load within different subsets of CD4 T
lymphocytes, were investigated in 16 patients with documented primary HIV infection. Four out of 16 subjects had also primary CMV infection
Results: HIV-1- and CMV-specific IFNg secreting CD4 T cells were consistently
detected in patients with primary and chronic HIV-1 and CMV co-infection and
were mostly contained in the cell population lacking expression of CCR7. Lymphoproliferative responses, however, were rarely observed. The magnitude of the
primary CMV-specific CD4 T cell response was significantly greater (mean %
IFNg secreting CD4 T cells 7.2) compared to the that of the primary HIV-1-specific
CD4 T cell response (mean % IFNg secreting CD4 T cells 0.49, P=0.003) and to
that observed in patients with chronic CMV infection (mean % 1.1, P=0.005). Of
interest, there were no differences in the magnitude of the CD4 T cell response
during primary and chronic HIV-1 infections (P=0.1). The analysis of viral load
in CD4+CCR7+ and CD4+CCR7- T cell populations indicated that a substantial
proportion of CD4+CCR7- T cells, i.e. the T cell population containing most of
HIV-1-specific CD4 T cells with effector function, were infected with HIV-1
Conclusions: These results indicate that the early and preferential infection of
HIV-1-specific CD4 T cells may prevent the generation of a robust CD4 T cell
immune response during primary infection and may help to explain the rapid impairment of HIV-1-specific CD4 T cell response
Presenting author: Alexandre Harari, Laboratory of AIDS Immunopathogenesis,
Hopital Beaumont-CHUV, 29 Av. Beaumont, 1011 Lausanne, Switzerland, Tel.:
[phone], Fax: [phone], E-mail: [email protected]
ThPeA7165 Colon eosinophilia in HIV-infected patients
A.L. Werneck-Silva', I.B. Prado2. Casa da AIDS, Infectious Diseases Division,
School of Medicine, University of Sao Paulo, Rua Harmonia 662apt23, CEP
05435-000, Sao Paulo, Brazil; 2 Gastroenterology Department, School of
Medicine, University of Sao Paulo, Sao Paulo, Brazil
Background: HIV-infected patients frequently have peripheral blood eosinophilia.
However, colon restricted eosinophilia has never been reported. We describe a
group of 16 HIV-infected patients with colon restricted eosinophilia.
Methods: 58 (44 men and 14 women), 41~9 years old, HIV-infected patients
with chronic diarrhea, underwent colonoscopy with multiple biopsies. Exclusion
criteria were atopic and/or skin disease, presence of enteropathogenic bacteria
or parasites in stool especimens and nonesteroidal anti-inflammatory drug use.
Tissue samples were examined after haematoxilin-eosin staining. Blood CD4 T
cells and eosinophils were measured.
Results: Colonoscopy was normal in all patients. Histological examination revealed chronic colitis (mainly mild) in all of them. Increased colonic eosinophil
infiltration was seen in 23 patients (group A). Only 7 out of these patients had
also blood eosinophilia (>600 cells/mm3). CD4T cell count was similar between
these 2 subgroups (p=0.4984). The remaining 35 patients had no blood or colon
eosinophilia (group B). Comparing groups A and B, there was no difference in
CD4T cell count (p=0.5057).
Conclusions: Our results demonstrate that colon eosinophilia is not dependent
on blood eosinophil count. These results suggest that local selective immunologic
mechanisms may be operating. It was demonstrated that eosinophils express
CD4 protein and that these cells bind HIV. It has also been shown that in vitro
stimulation of eosinophils by gpl20 HIV protein enhances eosinophil migration. It
is possible that colon eosinophilia we report here has been specifically induced
by HIV
Presenting author: Ana Luiza Werneck-Silva, Rua Harmonia 662apt23, CEP
05435-000, Sao Paulo, Brazil, Tel.: [phone], Fax: [phone], Email: [email protected]
ThPeA71 66 HIV patients responding to HAART display elevated
IL-5 production
N.M. Keane, P. Price, S. Lee, S.F. Stone, M.A. French. Department of Clinical
Immunology, Royal Perth Hospital and the Department of Pathology, University
of Western Australia, Department of Clinical Immunology, Royal Perth Hospital,
Wellington Street, Perth WA 6000, Australia
Background: HAART increases CD4+ T-cell counts and decreases viral load in
most HIV patients, but cell mediated immunity remains impaired. We hypothesise
that Typel/Type2 cytokine imbalance in HIV patients may explain this dysregulation. We evaluated Ti (IFNy) and T2 (IL-5) cytokines and soluble markers (CD26
DPPIV and sCD30, respectively) in a cross sectional study of a West Australian
HIV-1 cohort.
Methods: Peripheral blood mononuclear cells producing IFNy and IL-5 were enu
merated by ELISpot after overnight stimulation with mitogen. Cell culture supernatents were also assayed for IFNy and IL-5 production. Serum soluble CD30
and CD26 (DPPIV) levels were assayed by ELISA. Cytokine markers were compared with clinical indices of HIV disease, CD4+ T-cell count, CD8+ T-cell count,
eosinophil count and HIV viral load.
Results: HIV patients produced higher levels of IL-5 (median 57pg/ml) in cell culture supernatents compared to healthy controls (median 9pg/ml) after overnight