Claudia Cicala, Ph.D.

Laboratory of Immunoregulation

National Institute of Allergy and Infectious Diseases

National Institutes of Health

Bethesda, MD - USA

Role for Integrin α4β7+ in HIV and SIV Transmission and Pathogenesis?

Trafficking of HIV out of the mucosa

Ivor S. Douglas, Themistocles J Clin Invest. 2007;117(9):2391-2395.

• a4b7 is a cell-surface receptor expressed on T, B and NK cells. (GALT)

• a4b7 binds to MAdCAM, an adhesion receptor that is primarily expressed on HEV’s in GALT.

• The tissue-specific expression of MAdCAM in GALT defines a4b7 as the gut-homing receptor

Integrin α4β7 : gut homing receptor

Susceptibility of the GI Tract to SIV and HIV

1998

2003

2004

Gastrointestinal Tract as a Major Site of CD4+

T Cell Depletion and Viral Replication in SIVInfection

Ronald S. Veazey, MaryAnn DeMaria, Laura V. Chalifoux,Diniel E. Shvetz, Douglas R. Pauley, Heather L. Knight,

Michael Rosenzweig, R. Paul Johnson, Ronald C. Desrosiers,Andrew A. Lackner*

Journal of Virology, Nov. 2003, p. 11708-117170022-538X/03/$08.00+0 DOI: 10,1128/JVI,77,21.11708-11717,2003Copyright @ 2003, American Socety for Microbiology. All Rights Reserved.

Severe CD4+ T-Cell Depletion in Gut Lymphoid Tissue duringPrimary Human Immunodeficiency Virus Type 1 Infection

and Substantial Delay in Restoration following HighlyActive Antiretroviral Therapy

Moraima Guadalupe,1 Elizabeth Reay,1 Sumathi Sankaran,1 Thomas Prindiville,2

Jason Flamm,3 Andrew McNeil,2,4 and Satya Dandekar1,2*

Primary HIV-1 Infection Is Associated with Preferential

Depletion of CD4+ T Lymphocytes from Effector Sites

in the Gastrointestinal Tract

Saurabh Mehandru,1 Michael A. Poles,1,2 Klara Tenner-Racz,3

Amir Horowitz,1,2 Arlene Hurley,1 Christine Hogan,1 Daniel Boden,1

Paul Racz,3 and Martin Markowitz1

Vol. 77, No. 21

CD4+ T cells are preferentially depleted in the GI tract in acute and early HIV-1 infection

GI CD4+ T cells harbor a higher viral burden compared to peripheral blood CD4+ T cells

Lack of reconstitution in GI derived CD4+ T cells during prolonged ART in the majority of patients

Persistent Depletion of CD4+ T cells in the GI Tract Despite Normalization in the Peripheral Blood in ART-treated Patients

Primary HIV-1 Infection Is Associated with PreferentialDepletion of CD4+ T Lymphocytes from Effector Sitesin the Gastrointestinal Tract

Saurabh Mehandru,1 Michael A. Poles,1,2 Klara Tenner-Racz,3

Amir Horowitz,1,2 Arlene Hurley,1 Christine Hogan,1 Daniel Boden,1

Paul Racz,3 and Martin Markowitz1

Mechanisms of Gastrointestinal CD4+ T-Cell Depletion during Acuteand Early Human Immunodeficiency Virus Type 1 InfectionSaurabh Mehandru,1 Michael A. Poles,1,2 Klara Tenner-Racz,3 Victoria Manuelli,1 Patrick Jean-Pierre,1

Peter Lopez,1 Anita Shet,1 Andrea Low,1 Hiroshi Mohri,1 Daniel Boden,1

Paul Racz,3 and Martin Markowitz,1*

Lack of Mucosal Immune Reconstitutionduring Prolonged Treatment of Acute and EarlyHIV-1 InfectionSaurabh Mehandru1, Michael A. Poles1,2, Klara Tenner-Racz3, Patrick Jean-Pierre1, Victoria Manuelli1, Peter Lopez1,Anita Shet1, Andrea Low1, Hiroshi Mohri1, Daniel Boden1, Paul Racz3, Martin Markowitz1*

J. Exp. Med. 2004

JOURNAL OF VIROLOGY, 2007

PLoS MEDICINE 2006

• The GI tract is preferentially targeted during acute/early HIV-1

and SIV infections with consequent damage to the gut.

• In the majority of patients, long term antiretroviral therapy does

not efficiently reconstitute mucosal CD4+ T cells.

Key points

Integrin α4β7 and HIV Infection

natureimmunology

HIV-1 envelope protein binds to and signals throughintegrin a4b7, the gut mucosal homing receptor forperipheral T cellsJames Arthros1,6, Claudia Cicala1,6, Elena Martinelli1,2,6, Katilyn Macleod1, Donald Van Ryk1, Danlan Wei1,

Zhen Xiao3, Timothy D Veenstra3, Thomas P Conrad3, Richard A Lempicki4, Sherry McLaughlin5,

Massimiliano Pascuccio1, Ravindra Gopaul1, Jonathan McNally1, Catherine C Cruz1, Nina Censoplano1,

Eva Chung1, Kristin N Reitano1, Shyam Kottilil1, Diana J Goode1, & Anthony S Fauci1

Integrin α4β7 is the gut-homing receptor

a4b7+/CD4+ T cells define a subset of CD4+ T cells that are metabolically active, Ki67+,

CCR5high, CXCR4low.

The integrin a4b7 forms a complex with cell-surfaceCD4 and defines a T-cell subset that is highlysusceptible to infection by HIV-1Claudia Cicalaa,1,2, Elena Martinellia,1, Johnathan P. McNallya,1, Diana J. Goodea, Ravindra Gopaula, Joseph Hiatta,Katija Jelicica, Shyamasundaran Kottillila, Katilyn Macleoda, Angeline O’Sheaa, Nikita Patela, Donald Van Ryka,Danian Weia, Massimiliano Pascuccioa, Ling Yib, Lyle McKinnonc, Preson Izullad, Joshua Kimanid, Rupert Kaulc,Anthony S. Faucia,2, and James Arthosa

PN

AS

aLaboratoryofImmunoregulationand

bLaboratoryofMolecularImmunology,NationalInstituteofAllergyandInfectious

Diseases,NationalInstitutesofHealth,Bethesda,MD20892;cDepartmentofMedicine,UniversityofToronto,Toronto,

CanadaM5S1A8;anddDepartmentofMedicalMicrobiology,UniversityofNairobi,P.O.Box30197-00100,Kenya

a4b7+/CD4+ T cells appear in the gut and genital mucosa.

Memory Peripheral and Genital Tract a4b7high Memory CD4+ T

Cells Express CCR5 and are Highly Activated.

CD45RO CCR5 Ki-67

CD4+ T cells purified from peripheral blood and cultured in retinoic acid.

b7

• Naïve CD4+ T cells express an intermediate level of a4b7

• Memory CD4+ T cells express high levels of a4b7: a4b7 high CD4+ T cells

Preferential depletion of a4b7

high CD4+ T cells• intracellular p24 staining of CD4+ T cells, day

3, 6, 8, post infection

100 101 102 103 104100

101

102

103

104

0.82

1662

21.1

P24

Day 3

100 101 102 103 104100

101

102

103

104

38.7 27.1

7.826.4

100 101 102 103 104100

101

102

103

104

36.1 18.9

11.733.2

Day 8Day 6

b7

Sexual Transmission of HIV-1 is Inefficient

Result: the overall rate of HIV transmission observed in these discordant couples: 0.0012/coital act.

Potential barriers to HIV transmission across the genital mucosa.

Monaco et al. (2017) Current Topics in Microbiology and Immunology

“The entering viruses must interact with susceptible CD4+ CCR5+ T cellsto propagate since entry into non

permissive resting CD4+ T cells will result in nonproductive infection”

a4b7+/CD4+ T Cells are a Prime Target for Productive Infection

in Mucosal Tissues

100

75

50

25

0

%C

D6

9+C

D4

+T

ce

lls

a4b7+ a4b7

–

P<0.0001

100

75

50

25

0

%C

D4

ce

rvic

al T

ce

lls

a4b7hi a4b7

int 40.00 50.00 60.00 70.00 80.00 90.00 100.00

%CCR5 on a4b7+ CD4+ T cells

a4b

7/M

FI

2500.002000.001500.00

1000.00

500.00

r = 0.565P = 0.009

Cervical Cytobrush CD4 T Cells:

Characterization of a Human Cervical CD4+ T Cell Subset

Coexpressing Multiple Markers of HIV Susceptibility

Lyle R. McKinnon,*,† Billy Nyanga,†,1 Duncan Chege,*,1 Preston Izulla,† Makobu Kimani,†

Sanja Huibner,* Lawrence Gelmon,†, ‡ Katharine E. Block,§ Claudia Cicala,§

A. Omu Anzala,†,¶ James Arthos,§ Joshua Kimani,†,‡ and Rupert Kaul*,†,II

The Journal of Immunology, 2011, 187

Th17 Cells Are Preferentially Infected Very Early after Vaginal

Transmission of SIV in Macaques

Cell Host & Microbe Volume (2016)

Daniel J. Stieh, Edgar Matias, Huanbin Xu, Angela J. Fought, James L. Blanchard, Preston A. Marx, Ronald S. Veazey,

Thomas J. Hope

HSV2 Infection Upregulates α4β7 on the Surface of CD4+ T Cells

Martinelli et al PLoS Path 2011 Shannon et al J Immunol 2014

40

30

20

10

0

% a

4b

7+/C

D4

+T

cells

p < 0.001

HSV-2 Negative

HSV-2 Positive

Epithelium

HSV-2

HIV-1

RA?

R>1

CXCL10? IL7?

a4b7?

Gut andMLN

0

0 H

• Mucosal Immunol. 2009 Sep;2(5):439-49

• a4b7high CD4+ memory T cells harbor most Th-17 cells and are preferentially infected during acute SIV infection

• M Kader, X Wang, M Piatak, J Lifson, M Roederer, R Veazey and JJ Mattapallil.

• Mucosal Immunol. 2009 Sep;2(6):518-26

• Monitoring a4b7 integrin expression on circulating CD4+ T cells as a surrogate marker for tracking intestinal CD4+ T-cell loss

in SIV infection

• X Wang, H Xu, AF Gill, B Pahar, D Kempf, T Rasmussen, AA Lackner and RS Veazey.

• J Immunol. 2011 Jan 15;186(2):1044-59

• Blocking of Gut-Homing Integrin during Acute Infection Leads to Decreased Plasma and Gastrointestinal Tissue Viral Loads in Simian

Immunodeficiency Virus-Infected Rhesus Macaques

• Ansari A, Reimann K, Mayne A, Takahashi Y, Stephenson S, Wang R, Wang X, Li J, Price A, Little D, Zaidi M, Lyles R and Villinger F.

a4b7+/CD4+ T Cells are Targeted in Acute Infection

• Blood. 2001 Nov;98(10): 3169-3171

• Preferential and persistent depletion of CCR5+ T-helper lymphocytes with nonlymphoid homing potential despite early

treatment of primary infection

• R Krzysiek, A Rudent, L Bouchet-Delboe, A Foussat, C Boutillon, A Portier, D Ingrand, D Seveni, P Galanaud, L Grangeot-Karoe, D Emile

and the ANRS O86 PRIMOFERON A Study Group.

6

0

4

2

% o

f a

4b

7+

Ki6

7+

CD

4+

T C

ells

0 111 102 93 84 75 6Number of IR Challenges

R = –0.62

P = 0.02

The Frequency of α4β7hi Memory CD4+ T Cells is Directly

Correlated with Risk of Acquisition in Rhesus Macaques

J Acquir Immune Defic Syndr. 2013

The Frequency of a4b7high Memory CD4+ T Cells Correlates

With Susceptibility to Rectal Simian ImmunodeficiencyVirus Infection

Elena Martinelli, PhD, MPH,* Filippo Veglia, PhD,* Diana Goode, PhD,* Natalia Guerra-Perez, PhD,*

Meropi Aravantinou, MS,* James Arthos, PhD,† Midhael Piatak, Jr., DMV, PhD,‡ Jeffery D. Lifson, MD,‡

James Blanchard, PhD,§ Agegnehu Gettie, BS,II and Melissa Robbiani, PhD*

Adjuvant-dependent innate and adaptive immunesignatures of risk of SIVmac251 acquisition

Monica Vaccari1,23, Shari N Gordon1,23, Slim Fourati2,23, Luca Schifanella1,3,23, Namal P M Livanage1,23 & Genoveffa Franchini1,23

2016 NATURE MEDICINE

Effect of ART on Colonic α4β7hi CD4+ T Cells

50

0

40

10

30

20

HIV– CHIBaseline 24 mo6 mo 6 mo24 mo Baseline

Fiebig I Fiebig III

% C

D4

+b

7h

i(c

olo

n)

****

***

Colonic α4β7hi CD4+ T cells are not replenished, even after ART treatment

initiated in Fiebig I

0

100

20

60

40

HIV– baseline 6 mo 24 mo

Fiebig I

% C

D4

+C

CR

5+

(co

lon

)

Fiebig III

80

baseline 6 mo 24 mo CHI0

40

10

30

20

HIV– baseline 6 mo 24 mo

Fiebig I

% C

D4

+C

CR

5+

(PB

)

Fiebig III

baseline 6 mo 24 mo CHI

α4β7hi CD4+ T cells CCR5+ CD4+ T cells

Question

Can Targeting a4b7+ T cells have an

effect on SIV/HIV transmission ?

Rhesus Anti-a4b7 Antibody (mAb Act1)

Light

Chain

Hinge

Heavy chain

Mouse IgG Rhesus IgG1

Vedolizumab as Induction and Maintenance Therapy for Crohn's

Disease

William J. Sandborn, M.D., Brian G. Feagan, M.D., Paul

Rutgeerts, M.D., Ph.D., Stephen Hanauer, M.D., Jean-

Frédéric Colombel, M.D., Bruce E. Sands, M.D., Milan

Lukas, M.D., Ph.D., Richard N. Fedorak, M.D., Scott

Lee, M.D., Brian Bressler, M.D., Irving Fox, M.D., Maria

Rosario, Ph.D., Serap Sankoh, Ph.D., Jing Xu, Ph.D.,

Kristin Stephens, B.A., Catherine Milch, M.D., and Asit

Parikh, M.D., Ph.D., for the GEMINI 2 Study Group

Vol. 369 August 22, 2013 No. 8

Vedolizumab is a human analogue of mAb Act1

α4β7 mAb Protects Rhesus Macaques From aLow-dose Mucosal Challenge

Targeting a4b7 integrin reducesmucosal transmission of simianimmunodeficiency virus andprotects gut-associated lymphoidtissue from infectionSiddappa N Byrareddy1,8, Brianne Kallam1,8, James Arthos2,

Claudia Cicala2, Fatima Nawaz2, Joseph Hiatt2, Ellen N Kersh3,

Janet M McNicholl3, Debra Hanson3, Keith A Reimann4,

Markus Brameier5, Lutz Walter5, Kenneth Rogers6, Ann E Mayne1,

Paul Dunbar1, Tara Villinger1, Dawn Little1, Tristram G Parslow1,

Philip J Santangelo7, Francois Villinger1,6, Anthony S Fauci2 &

Aftab A Ansari1

medicinenature

25---0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24

α4α7 mAb or normal IgGIntravaginal infection

mAb mAb mAb mAb

Viralchallenges

Week

Low-DoseChallengeStudyDesign

α4α7 mAb monkeys

control mAb monkeys

α4β7 mAb prevents and delays mucosal transmission of SIV

Significant protection

Pronounced delay in viremia

1.0

0.8

0.6

0.4

0.2

0.0

Fra

ction o

f R

Ms r

em

ain

ing u

nin

fecte

d

0 1 2 3 4 5 6 7 8 9 10

Time after initial SIVmac251 challenge (weeks)

a4b7 mAb

IgG treated RMs

P = 0.002

Individual Plasma Viremia Levels in NHPs Receiving Either α4β7

mAb or Control IgG During Mucosal Challenge with SIVmac251

0

8

2

6

4

0 4 168 12

Time after Initial SIVmac251 Challenge (weeks)

Lo

g p

lasm

a v

ira

l R

NA

(cop

ies/m

l)

IgG ControlAnti-a4b7+ Antibody

PWw

RCw11

RDg11

RFk11

Rlz12

RLn12

ROc11

RQf10

RRc9

RRq9

Rlv7

RQm11

RBs9

REo8

RHy12

Rlq9

RKs11

RLc12

RRn11

RTm11

RVw10

RWt9

RZz10

RCd12

0 4 168 12

6/12 infected 10/12 infected

α4β7 mAb Protects the Gut

pro-viral DNA levels in gastro-intestinal tissue biopsies

anti- a4b7 treated/infected IgG treated/infected 40

30

20

10

0

Vira

l D

NA

(co

pie

s/n

g)

4 8 12 16

Time after initial SIVmac251 challenge (weeks)

40

30

20

10

04 8 12 16

Time after initial SIVmac251 challenge (weeks)

Vira

l D

NA

(cop

ies/n

g)

RCw11

RDg11

RIz12

ROc11

RRc9

RQm11

RBs9

REo8

RHy12

RKs11

RLc12

RRn11

RVw10

RWt9

RZz10

RCd12

Anti a4b7 Minimizes Loss of Both Memory and Naïve CD4+ T Cells in the Peripheral Blood

1500

1000

500

00 4 8 12 16

750

500

250

00 4 8 12 16

750

500

250

00 4 8 12 16 0 4 8 12 16

75

50

25

0

Absolu

te C

D4

+T

cells

Centr

al m

em

ory

CD

4+

T c

ells

Naïv

e C

D4+

T c

ells

Eff

ecto

r m

em

ory

CD

4+

T c

ells

P < 0.001

P = 0.58

P = 0.04

P = 0.02

CD4+ T cells (total)

Central memory CD4+ T cells Effector memory CD4+ T cells

Naïve CD4+ T cells

uninfected RMs

anti-α4β7 treated infected RMs

IgG treated infected RMs

Protection of gut tissue preserves peripheral CD4+ T cells

pro-viral DNA levels in gastro-intestinal tissue biopsies

anti-α4α7 treated/infected IgG treated/infected 40

30

20

10

0

Vir

al D

NA

(co

pie

s/n

g)

4 8 12 16

Time after initial SIVmac251 challenge (weeks)

40

30

20

10

04 8 12 16

Time after initial SIVmac251 challenge (weeks)

Vir

al D

NA

(co

pie

s/n

g)

RCw11

RDg11

RIz12

ROc11

RRc9

RQm11

RBs9

REo8

RHy12

RKs11

RLc12

RRn11

RVw10

RWt9

RZz10

RCd12

Lo

g p

lasm

a v

ira

l R

NA

(cop

ies/m

l)

Anti-a4b7+ Antibody

1500

1000

500

00 4 8 12 16

750

500

250

00 4 8 12 16

750

500

250

00 4 8 12 16 0 4 8 12 16

75

50

25

0

Absolu

te

CD

4+

T c

ells

Centr

al

mem

ory

CD

4+

T c

ells

Naïv

e C

D4+

T c

ells

Effecto

r m

em

ory

CD

4+

T c

ells

P < 0.001

P = 0.58

P = 0.04

P = 0.02

CD4+ T cells (total)

Central memory CD4+ T cells Effector memory CD4+ T cells

Naïve CD4+ T cells

Transverse Colon

Small

Bowel

Descendin

g Colon

Axillary LN

Small

Bowel

Descendin

g Colon

Inguinal

LN

Spleen

Descendin

g Colon

Inguinal

LN

Transverse ColonTransverse Colon

Descendin

g Colon

Small

Bowel

Small

Bowel

CT PET/CT fusion

Probes

Immuno-PET/CT Interrogation of SIV Infected Macaques

1. 64Cu-labeled anti-CD4 F(ab’)2

2. 64Cu-labeled anti-gp120

Immuno-PET/CT Interrogation of SIV Infected Macaques

IgG treated α4β7 mAb treated

Spleen Ing LN Ax LN Lung Colon Smallbowel

GenitalTract

0.0

0.2

0.4

0.6

0.8

1.0

SU

Vm

ax

IgG/7D3

α4β7 mAb/7D3

Probe 64Cu-labeled anti-gp120

3 weeks post-infection

a4b7 mAb treatment reduced virus in gut, but also in other lymphoid tissues

α4β7 mAb treated

IgG treated

1. A primatized monoclonal IgG antibody directed against a4b7 reduces the efficiency of vaginal transmission of SIV in rhesus macaques.

2. a4b7highCD4+ T cells that reside in, or traffic to, the gut-

associated lymphoid tissues (GALT) play a key role in SIV transmission.

3. In macaques that do become infected in the presence of an a4b7 mAb, viremia is delayed and GALT is protected in a significant way

Conclusions

Question

Can Targeting a4b7+ T cells

change the pathogenesis of

SIV/HIV infection?

Schema of Experimental Design ART + anti-α4β7 Study

anti-a4b7 Treated Group (n=11)

Weeks

Baseline

collections

SIVmac239

(200TCID50)

ART administered

daily for 3 months

ART administration

terminated

0 4 5 8 9 12 16 18 8020 7024 6028 5032 4036

PMPA (20mg/kg/day) SubQ

FTC (50mg/kg/day) SubQ

Integrase inhibitor L-870812 (100mg/kg/day) Oral

anti-IgG Treated Group (n=7)

ART

a4b7 or IgG

Administration terminated

a4b7 or IgG (50mg/kg)

Administration initiated

Combining ART with anti-a4b7 Promotes Virologic Control in SIV Infected Macaques

Weeks

Baselinecollections

SIVmac239

(200TCID50)

ART administered

daily for 3 months

ART administration

terminated

0 4 5 8 9 12 16 18 8020 7024 6028 5032 4036

PMPA (20mg/kg/day) SubQ

FTC (50mg/kg/day) SubQ

Integrase inhibitor L-870812 (100mg/kg/day) Oral

anti-a4b7 or IgG

8

0

6

2

4

0 505 4510 4015 3520 3025

60

20

50

30

40

0 505 4510 4015 3520 30250

10

Log Plasma Viral RNA (copies/ml) Pro-viral DNA levels in gastro-intestinal tissue

biopsies(copies/ng DNA) (Geometric mean)

ART****

ART

****

a4b7

IgG

a4b7

IgG

Phase I Phase II Phase III Phase IV Phase V Phase I Phase II Phase III Phase IV Phase V

ART + anti-a4b7 Treatment Promotes the Restoration of CD4+ T Cells in SIV Infected Macaques

4000

0

3000

2000

1000

0 5010 4020 30

To

tal C

D4

+T

Ce

ll (A

bs #

)

80

0

60

40

20

0 5010 4020 30

To

tal C

D4

+T

Ce

lls

PBMC GUT

********

ART + anti-a4b7

ART alone

Blood CD4 counts indicate absolute cell numbers.

Gut CD4 frequencies based on gated population of CD45+ cells.

CD4+ Cell PET imaging of animals treated with combination ART + a4b7 mAbRId14 (a4b7 mAb) RIt11 (IgG)

NA

LT

an

d F

acia

l

Cra

nia

l L

N

Ga

str

oin

testina

l

Tra

ct

Axill

ary

LN

Ing

uin

al L

N

1.5

0.0

1.0

0.1

SU

V

0.80

0.00

0.70

0.10

0.60

0.20

0.50

0.30

0.40

NALT MuscleFacial

cranial LN

Inguinal

LN

Axillary

LN

SU

Vm

ax

a4b7 mAb

IgG

0.00

3.00

0.50

2.50

1.00

2.00

1.50

SU

Vm

ax

Spleen Muscle MuscleGut

a4b7 mAb

IgG

0.30

0.00

0.25

0.05

0.20

0.10

0.15

SU

Vm

ean

ART + a4b7 mAb Promotes Durable Preservation of CD4+

cells in Gut and Lymphoid Tissues

week 50 week 50

Durable Control of Viremia and Durable Preservation of CD4 cells inART + a4b7 mAb treated Macaques

8

0

6

2

4

60 8070

Time after initial SIVmac239 challenge

(weeks)

Lo

g p

lasm

a v

ira

l R

NA

(co

pie

s/m

l)

8

0

6

2

4

60 8070

Time after initial SIVmac239 challenge

(weeks)

Lo

g p

lasm

a v

ira

l R

NA

(co

pie

s/m

l)

8

0

6

2

4

60 8070

Time after initial SIVmac239 challenge

(weeks)

Lo

g p

lasm

a v

ira

l R

NA

(co

pie

s/m

l)

RId14

RLn12

ROo13

RSd14

RDa15

RFa15

ROq14

ROv14

RBe14 †

RIt11 †

RKs13 †

RSy13 †

RYy13 †

RLo14

RUs14

a4b7 mAb treated

IgG treated RMs

Immuno-histological evaluation of CD4+ T cells in GIT biopsy specimens

ART + IgG ART + a4b7 mAb

Combination ART + a4b7 mAb reduces gut viral load over ART alone during the dual-therapy (aviremic) phase.

smal

l bow

el

larg

e in

test

ine

sple

en

axill

ary

LN

inguin

al L

Nlu

ng

NALT

musc

le0.0

0.1

0.2

0.3

0.4

0.5

0.6

SU

V m

ax

a4b7 IgG

SIV gp120 PET imaging

a4b7+/CD4+ T Cells are a Prime Target for Productive Infection

in Mucosal Tissues

Acknowledgements

EMORY UNIV.ANN E. MAYNE

DAWN LITTLE

KRISTINA ORTIZ

NEIL SIDELL

A. A. ANSARI

NIAIDCLAUDIA CICALA

DONALD VAN RYK

KATIJA JELICIC

DANLAN WEI

ANTHONY S. FAUCIYERKES PRIMATE CTR

PRAVEEN K. AMANCHA

SANJEEV GUMBER

GERMAN PRIMATE CTRLUTZ WALTER

CHRISTIAN ROOS

ANGELA NOLL

GEORGIA TECHPHILIP SANTANGELO

CHIARA ZURLA

UNIV. OF MARYLANDMAUREEN KANE

JIANSHI YU

JACE W. JONES

DEPT PATH EMORY UNIVTRISTRAM G. PARSLOW

MICHELLE D. REID

VOLKAN ADSAY

UNIV. OF MICHIGANKELLY B. ARNOLD

CAROLINE E. WOODY

JOHNS HOPKINS UNIVRAFFAELLO CIMBRO

UNIV OF MANITOBALYLE R. MCKINNON

AIDA SIVRO

MHRPMERLIN ROBB

JINTANAT ANAWORANICH

SHELLY KREBS

UNIV OF TORONTORUPERT KAUL

NEW IBERIA RESEARCH CENTERFRANCOIS VILLINGER

MHRP-AFRIMSALEXANDRA SCHUETZ

UNIV OF NEBRASKASIDDAPPA BYRAREDDY

CAPRISALYLE MCKINNON

QUARRAISHA ABDOOL KARIM

SALIM ABDOOL KARIM

JO-ANN PASSMORE