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Clonal Dominance Patterns of CD8 T Cells in Relation to Disease Progression in HIV-Infected Children

Soe Than, Monica Kharbanda, Vivek Chitnis, Saroj Bakshi, Peter K. Gregersen and Savita Pahwa
J Immunol March 15, 1999, 162 (6) 3680-3686;
Soe Than
*Division of Allergy/Immunology, Department of Pediatrics and
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Monica Kharbanda
*Division of Allergy/Immunology, Department of Pediatrics and
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Vivek Chitnis
*Division of Allergy/Immunology, Department of Pediatrics and
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Saroj Bakshi
*Division of Allergy/Immunology, Department of Pediatrics and
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Peter K. Gregersen
†Division of Biology and Human Genetics, Department of Internal Medicine, North Shore University Hospital, New York University School of Medicine, Manhasset, NY 11030
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Savita Pahwa
*Division of Allergy/Immunology, Department of Pediatrics and
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  •            FIGURE 1.
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    FIGURE 1.

    TCR Vβ repertoire in CD8 cells from normal cord blood: Immunoscope pattern shows no clonal dominance. A–L indicate reaction sets of multiplex PCRs (see Table II).

  •            FIGURE 2.
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    FIGURE 2.

    Representative immunoscope pattern of CD8 TCR Vβ repertoire showing major clonal dominance in CD8 cells from an HIV-infected child. Arrowheads indicate dominant clones that appear as single peaks to reflect clonal dominance in affected Vβ families. A–L indicate reaction sets of multiplex PCRs (see Table II).

  •            FIGURE 3.
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    FIGURE 3.

    Lymphoproliferative responses in HIV-infected children. LPAs were performed with PBMCs as described in Materials and Methods. Patient group 1 = major/minor clonal dominance; patient group 2 = single/no clonal dominance. ∗, Mean stimulation index values in group 1 were significantly higher than in group 2 (p = 0.002 for Candida and tetanus responses and p < 0.001 for responses to alloantigens).

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    FIGURE 4.

    Correlation between the number of CD8 TCR Vβ-dominant clones and the percentage of CD4 cells in HIV-infected children (r = 0.669, p < 0.001).<./>

  •            FIGURE 5.
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    FIGURE 5.

    Correlation between the number of CD8 TCR Vβ-dominant clones and plasma HIV RNA in HIV-infected children. There is no statistically significant correlation (r = −0.236, p = 0.285).

Tables

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    Table I.

    Age, immunological, and virological characteristics and treatment of patients

    Subject ID No.Pattern of DominancecDominant Vβ Family(s)HIV RNA Copies/ml (log10)Age (yr)CDC ClassCD4 %CD8 %ARTa
    Group 1
    964Major4, 1, 12, 22<200 (<2.3)1.1N13132Yes
    860Major1, 2, 3, 5.2, 7, 22, 11, 1543,575 (4.6)1.6C13445Yes
    677Major5.1, 15, 99,408 (3.9)4B14035Yes
    121Major19, 5.1, 5.2, 11, 12, 89,068 (3.9)5C12542Yes
    117bMajor23, 2, 14, 24, 16, 958,812 (4.9)7N14333No
    569Major2, 14, 21, 15648,678 (5.8)8.4B3358Yes
    804bMajor2, 5.1, 7, 17, 1420,160 (4.3)9N13037No
    113Major24, 3, 13.1, 16, 201,486 (3.1)11B12644Yes
    129Major6, 7, 174,574 (3.6)13A13746Yes
    988Major18, 3, 19, 14394,156 (5.6)13.5A31023Yes
    1075Minor2, 5.21,039 (3.0)0.75N13022Yes
    114Minor6, 2276,509 (4.8)5.4C13042No
    Group 2
    992Single189,639 (4.9)7.5B3967Yes
    658Single1850,099 (4.6)8.3B3247Yes
    109Single767,037 (4.8)9.4B3734Yes
    1028None—25,571 (4.4)5.4B3728Yes
    124None—131,924 (5.1)6.0B31756Yes
    108None—53,772 (4.7)9.6B3965Yes
    029None—21,888 (4.3)10.4B31221Yes
    675None—2,022 (3.4)12.6B31448Yes
    780None—531,429 (5.7)14A3750Yes
    962None—94,356 (4.9)15C3259Yes
    • a ART with dual or triple drug combinations including AZT, 3TC, ddI, d4T, Nevirapine, and the protease inhibitors Nelfinavir, Ritonavir, and Saquinavir.

    • b Patients identified as LTNPs.

    • c Major = three or more Vβ families involved, minor = two Vβ families, single = one Vβ family, none = no clonal dominance.

    • View popup
    Table II.

    Primer sequences for multiplex PCR

    PrimerSequencePositionReaction Seta
    Vβ15′-CAA CAG TTC CCT GAC TTG CAC-3′84A
    Vβ25′-TCA ACC ATG CAA GCC TGA CCT-3′86B
    Vβ35′-TCT AGA GAG AAG AAG GAG CGC-3′86C
    Vβ45′-CAT ATG AGA GTG GAT TTG TCA TT-3′122B
    Vβ5S15′-TTC AGT GAG ACA CAG AGA AAC-3′135D
    Vβ5S25′-CCT AAC TAT AGC TCT GAG CTG-3′75D
    Vβ65′-AGG CCT GAG GGA TCC GTC TC-3′81E
    Vβ75′-CTG AAT GCC CCA ACA GCT CTC-3′86F
    Vβ85′-TAC TTT AAC AAC AAC GTT CCG-3′144B
    Vβ95′-AAA TCT CCA GAC AAA GCT CAC-3′84G
    Vβ105′-CAA AAA CTC ATC CTG TAC CTT-3′76L
    Vβ115′-ACA GTC TCC AGA ATA AGG ACG-3′90H
    Vβ125′-GAC AAA GGA GAA GTC TCA GAT-3′117H
    Vβ13S15′-GAC CAA GGA GAA GTC CCC AAT-3′117C
    Vβ13S25′-GTT GGT GAG GGT ACA ACT GCC-3′135I
    Vβ145′-TCT CGA AAA GAG AAG AGG AAT-3′84J
    Vβ155′-GTC TCT CGA CAG GCA CAG GCT-3′87I
    Vβ165′-GAG TCT AAA CAG GAT GAG TCC-3′132G
    Vβ175′-CAC AGA TAG TAA ATG ACT TTC AG-3′137J
    Vβ185′-GAG TCA GGA ATG CCA AAG GAA-3′117A
    Vβ195′-CCC CAA GAA CGC ACC CTG C-3′79K
    Vβ205′-TCT GAG GTG CCC CAG AAT CTC-3′111E
    Vβ215′-GAT ATG AGA ATG AGG AAG CAG-3′143L
    Vβ225′-CAG AGA AGT CTG AAA TAT TCG A-3′122F
    Vβ235′-TCA TTT CGT TTT ATG AAA AGA TGC-3′146A
    Vβ245′-AAA GAT TTT AAC AAT GAA GCA GAC-3′129K
    Cβ145′-CTC AGC TCC ACG TG-3′
    CβR5′-CTT CTG ATG GCT CAA ACA C-3′
    • a A total of 12 reaction sets (A—L) with two or more primers were used for multiplex PCR, as described in Materials and Methods.

    • View popup
    Table III.

    Immunological and virological characteristics and lymphoproliferative responses of patients with major/minor or single/none pattern of CD8 clonal dominance

    Major + Minor (n = 12)Single + None (n = 10)p Values
    Age (yr)6.8 ± 4.49.8 ± 3.2NS
    V.L. (log10)a4.1 ± 1.14.8 ± 0.7NS
    % CD428.3 ± 11.68.6 ± 4.8<0.001
    % CD838.3 ± 10.147.5 ± 15.5NS
    DR+CD38+b37.4 ± 13.154.6 ± 14.2<0.01
    LPA
    PHA400.2 ± 518.5258.4 ± 144.7NS
    Candida 92.0 ± 59.512.3 ± 14.40.002
    Tetanus76.3 ± 51.211.2 ± 12.70.002
    MLC178.3 ± 298.932.9 ± 35.2<0.001
    • a V.L. = Plasma HIV RNA (log10)

    • b Expressed as % CD8 cells.

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The Journal of Immunology: 162 (6)
The Journal of Immunology
Vol. 162, Issue 6
15 Mar 1999
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Clonal Dominance Patterns of CD8 T Cells in Relation to Disease Progression in HIV-Infected Children
Soe Than, Monica Kharbanda, Vivek Chitnis, Saroj Bakshi, Peter K. Gregersen, Savita Pahwa
The Journal of Immunology March 15, 1999, 162 (6) 3680-3686;

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Clonal Dominance Patterns of CD8 T Cells in Relation to Disease Progression in HIV-Infected Children
Soe Than, Monica Kharbanda, Vivek Chitnis, Saroj Bakshi, Peter K. Gregersen, Savita Pahwa
The Journal of Immunology March 15, 1999, 162 (6) 3680-3686;
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