Blood T-cell receptor diversity decreases during the course of HIV infection, but the potential for a diverse repertoire persists.

Publisher: Elsevier Country of Publication: United States NLM ID: 7603509 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1528-0020 (Electronic) Linking ISSN: 00064971 NLM ISO Abbreviation: Blood Subsets: MEDLINE

Publication: 2021- : [New York] : Elsevier
Original Publication: New York, Grune & Stratton [etc.]

Genetic Variation/*physiology ; HIV Infections/*immunology ; HIV-1/*immunology ; Receptors, Antigen, T-Cell, alpha-beta/*genetics; Adult ; Aged ; CD4-Positive T-Lymphocytes/immunology ; CD4-Positive T-Lymphocytes/metabolism ; CD8-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/metabolism ; Cohort Studies ; Disease Progression ; Down-Regulation ; Female ; Follow-Up Studies ; Gene Rearrangement, T-Lymphocyte/genetics ; Gene Rearrangement, T-Lymphocyte/physiology ; HIV Infections/blood ; HIV Infections/genetics ; Humans ; Male ; Middle Aged ; Models, Biological ; Receptors, Antigen, T-Cell, alpha-beta/immunology ; Receptors, Antigen, T-Cell, alpha-beta/metabolism

HIV infection results in a decrease in circulating CD4(+) T-cell and naive T-cell numbers. If such losses were associated with an erosion of T-cell receptor (TCR) repertoire diversity in the peripheral T-cell pool, this might exacerbate the state of persistent immunodeficiency. Existing methods for the analysis of the TCR repertoire have demonstrated skewed distributions of TCR genes in HIV-infected subjects but cannot directly measure TCR diversity. Here we used AmpliCot, a quantitative assay based on DNA hybridization kinetics, to measure TCR diversity in a cross-sectional comparison of 19 HIV-infected persons to 18 HIV-uninfected controls. HIV-infected persons had a 10-fold decrease in total TCR repertoire diversity in 1.5 mL of blood compared with uninfected controls, with decreased diversity correlating most closely with a lower CD4(+) T-cell percentage. Nonetheless, the TCR repertoire diversity of sort-purified T-cell subpopulations in HIV-infected and HIV-uninfected subjects was comparable. These observations suggest that the TCR repertoire diversity changes in whole blood during HIV disease progression are primarily the result of changes in the number and proportion of T-cell subpopulations and that most HIV-infected persons may retain a sufficiently diverse TCR repertoire to permit immune reconstitution with antiretroviral therapy alone, without thymopoiesis.

J Infect Dis. 2001 Apr 15;183(8):1285-9. (PMID: 11262214)
Nature. 2002 May 2;417(6884):95-8. (PMID: 11986671)
J Immunol Methods. 2011 May 31;368(1-2):45-53. (PMID: 21385585)
AIDS Res Hum Retroviruses. 2000 Nov 20;16(17):1877-86. (PMID: 11118073)
J Exp Med. 2008 Mar 17;205(3):711-23. (PMID: 18332179)
Clin Immunol. 2005 May;115(2):138-46. (PMID: 15885636)
J Immunol. 2005 Jun 1;174(11):7446-52. (PMID: 15905594)
J Immunol. 2006 Feb 15;176(4):2645-53. (PMID: 16456027)
AIDS. 2002 May 24;16(8):1103-11. (PMID: 12004268)
JAMA. 2007 Jun 6;297(21):2349-50. (PMID: 17551128)
Science. 1996 Jun 21;272(5269):1755-62. (PMID: 8650574)
J Clin Invest. 1998 Jun 1;101(11):2301-8. (PMID: 9616201)
J Leukoc Biol. 2008 Jun;83(6):1382-7. (PMID: 18372341)
Nat Methods. 2006 Nov;3(11):895-901. (PMID: 17060913)
Gut Pathog. 2010 Mar 31;2(1):2. (PMID: 20356368)
J Clin Invest. 2009 Apr;119(4):997-1007. (PMID: 19287090)
J Exp Med. 2008 Jul 7;205(7):1701-14. (PMID: 18573906)
J Immunol. 2011 Apr 1;186(7):4285-94. (PMID: 21383244)
Blood. 2009 Nov 5;114(19):4099-107. (PMID: 19706884)
Ann Intern Med. 1997 Jun 15;126(12):946-54. (PMID: 9182471)
J Virol. 2001 Dec;75(24):11983-91. (PMID: 11711588)
J Immunol. 2002 Aug 15;169(4):1984-92. (PMID: 12165524)
J Virol. 2010 Oct;84(19):10354-65. (PMID: 20668079)
Nature. 2004 Dec 9;432(7018):769-75. (PMID: 15592417)
Immunity. 2003 Feb;18(2):193-204. (PMID: 12594947)
Nat Med. 1998 Feb;4(2):215-21. (PMID: 9461196)
AIDS. 1999 Feb 25;13(3):341-9. (PMID: 10199224)
J Virol. 2007 Jul;81(14):7759-65. (PMID: 17409149)
Clin Investig. 1992 Jul;70(7):539-44. (PMID: 1392422)
J Exp Med. 2007 Sep 3;204(9):2171-85. (PMID: 17724130)
J Infect Dis. 1998 Mar;177(3):579-85. (PMID: 9498435)
AIDS. 2001 Sep 28;15(14):1749-56. (PMID: 11579235)
N Engl J Med. 1990 Jan 18;322(3):161-5. (PMID: 1967190)
J Clin Invest. 1995 May;95(5):2061-6. (PMID: 7738173)
Clin Infect Dis. 2010 Sep 1;51(5):611-9. (PMID: 20645862)
Anal Biochem. 2011 Apr 1;411(1):106-15. (PMID: 21111699)
Genome Res. 2011 May;21(5):790-7. (PMID: 21349924)
J Immunol. 2010 Jun 15;184(12):6739-45. (PMID: 20483749)
AIDS. 2007 Aug 20;21(13):1711-5. (PMID: 17690568)
Blood. 2009 Jun 18;113(25):6304-14. (PMID: 19380868)
Immunol Lett. 2010 Sep 6;133(1):42-8. (PMID: 20621124)
N Engl J Med. 2010 Jan 21;362(3):270-1; author reply 271. (PMID: 20089981)
J Immunol. 1995 Nov 15;155(10):5046-56. (PMID: 7594513)
J Clin Invest. 2008 Mar;118(3):1085-98. (PMID: 18292808)
Nat Med. 1997 May;3(5):533-40. (PMID: 9142122)

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0 (Receptors, Antigen, T-Cell, alpha-beta)

Date Created: 20120229 Date Completed: 20120612 Latest Revision: 20211021

20231215

PMC3325037

10.1182/blood-2011-11-395384

22371879