Dynamics and Correlates of CD8 T-Cell Counts in Africans with Primary Human Immunodeficiency Virus Type 1 Infection

被引:2
|
作者
Prentice, Heather A. [1 ,13 ]
Lu, Hailin [1 ]
Price, Matthew A. [2 ,3 ]
Kamali, Anatoli [4 ]
Karita, Etienne [5 ]
Lakhi, Shabir [6 ]
Sanders, Eduard J. [7 ,8 ]
Anzala, Omu [9 ]
Allen, Susan [5 ,6 ,10 ]
Goepfert, Paul A. [1 ]
Hunter, Eric [11 ]
Gilmour, Jill [12 ]
Tang, Jianming [1 ]
机构
[1] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA
[2] Int AIDS Vaccine Initiat, New York, NY USA
[3] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA
[4] MRC UVRI Uganda Virus Res Unit AIDS, Masaka Site, Masaka, Uganda
[5] Project San Francisco, Kigali, Rwanda
[6] Zambia Emory HIV Res Project, Lusaka, Zambia
[7] Kenya Govt Med Res Ctr, Ctr Geog Med Res, Kilifi, Kenya
[8] Univ Oxford, Ctr Clin Vaccinol & Trop Med, Headington, England
[9] Kenya AIDS Vaccine Initiat, Nairobi, Kenya
[10] Emory Univ, Dept Pathol & Lab Med, Atlanta, GA 30322 USA
[11] Emory Univ, Vaccine Res Ctr, Atlanta, GA 30322 USA
[12] Chelsea & Westminster Hosp, Human Immunol Lab, Int AIDS Vaccine Initiat, London, England
[13] Kaiser Permanente, San Diego, CA USA
关键词
CD4CD8 LYMPHOCYTE RATIO; HIGHLY PATHOGENIC SIV; HIV-1; INFECTION; IMMUNE CONTROL; VIRAL LOAD; HLA; HOST; EXPRESSION; ESCAPE; GAG;
D O I
10.1128/JVI.01467-16
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
In individuals with HIV-1 infection, depletion of CD4(+) T cells is often accompanied by a malfunction of CD8(+) T cells that are persistently activated and/or exhausted. While the dynamics and correlates of CD4 counts have been well documented, the same does not apply to CD8 counts. Here, we examined the CD8 counts in a cohort of 497 Africans with primary HIV-1 infection evaluated in monthly to quarterly follow-up visits for up to 3 years in the absence of antiretroviral therapy. Statistical models revealed that (i) CD8 counts were relatively steady in the 3- to 36-month period of infection and similar between men and women; (ii) neither geography nor heterogeneity in the HIV-1 set-point viral load could account for the roughly 10-fold range of CD8 counts in the cohort (P>0.25 in all tests); and (iii) factors independently associated with relatively high CD8 counts included demographics (age <= 40 years, adjusted P = 0.010) and several human leukocyte antigen class I (HLA-I) alleles, including HLA-A*03:01 (P = 0.013), B*15:10 (P = 0.007), and B*58:02 (P<0.001). Multiple sensitivity analyses provided supporting evidence for these novel relationships. Overall, these findings suggest that factors associated with the CD8 count have little overlap with those previously reported for other HIV-1-related outcome measures, including viral load, CD4 count, and CD4/CD8 ratio. IMPORTANCE Longitudinal data from 497 HIV-1 seroconverters allowed us to systematically evaluate the dynamics and correlates of CD8(+) T-cell counts during untreated primary HIV-1 infection in eastern and southern Africans. Our findings suggest that individuals with certain HLA-I alleles, including A*03 (exclusively A*03: 01), persistently maintain relatively high CD8 counts following HIV-1 infection, a finding which may offer an intriguing explanation for the recently reported, negative association of A*03 with HIV-1-specific, broadly neutralizing antibody responses. In future studies, attention to HLA-I genotyping data may benefit in-depth understanding of both cellular and humoral immunity, as well as the intrinsic balances of these types of immunity, especially in settings where there is emerging evidence of antagonism between the two arms of adaptive immunity.
引用
收藏
页码:10423 / 10430
页数:8
相关论文
共 50 条
  • [1] Differentiation and Function of Follicular CD8 T Cells During Human Immunodeficiency Virus Infection
    Xiao, Minglu
    Chen, Xiangyu
    He, Ran
    Ye, Lilin
    FRONTIERS IN IMMUNOLOGY, 2018, 9
  • [2] Effects of exogenous interleukin-7 on CD8(+) T-cell survival and function in human T-cell lymphotropic virus type 1 infection
    White, Yohann
    Yoshimitsu, Makoto
    Kozako, Tomohiro
    Matsushita, Kakushi
    Koriyama, Chihaya
    Uozumi, Kimiharu
    Suzuki, Shinsuke
    Kofune, Hiroki
    Arima, Naomichi
    LEUKEMIA & LYMPHOMA, 2013, 54 (10) : 2243 - 2250
  • [3] Human Immunodeficiency Virus Type 1-Specific CD8+ T-Cell Responses during Primary Infection Are Major Determinants of the Viral Set Point and Loss of CD4+ T Cells
    Streeck, Hendrik
    Jolin, Jonathan S.
    Qi, Ying
    Yassine-Diab, Bader
    Johnson, Randall C.
    Kwon, Douglas S.
    Addo, Marylyn M.
    Brumme, Chanson
    Routy, Jean-Pierre
    Little, Susan
    Jessen, Heiko K.
    Kelleher, Anthony D.
    Hecht, Frederick M.
    Sekaly, Rafick-Pierre
    Rosenberg, Eric S.
    Walker, Bruce D.
    Carrington, Mary
    Altfeld, Marcus
    JOURNAL OF VIROLOGY, 2009, 83 (15) : 7641 - 7648
  • [4] T-Cell Correlates of Vaccine Efficacy after a Heterologous Simian Immunodeficiency Virus Challenge
    Martins, Mauricio A.
    Wilson, Nancy A.
    Reed, Jason S.
    Ahn, Chanook D.
    Klimentidis, Yann C.
    Allison, David B.
    Watkins, David I.
    JOURNAL OF VIROLOGY, 2010, 84 (09) : 4352 - 4365
  • [5] CD8 T-Cell Proliferative Capacity Is Compromised in Primary HIV-1 Infection
    Heath, Sonya L.
    Sabbaj, Steffanie
    Bansal, Anju
    Kilby, J. Michael
    Goepfert, Paul A.
    JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES, 2011, 56 (03) : 213 - 221
  • [6] Reevaluating the CD8 T-Cell Response to Herpes Simplex Virus Type 1: Involvement of CD8 T Cells Reactive to Subdominant Epitopes
    Sheridan, Brian S.
    Cherpes, Thomas L.
    Urban, Julie
    Kalinski, Pawel
    Hendricks, Robert L.
    JOURNAL OF VIROLOGY, 2009, 83 (05) : 2237 - 2245
  • [7] Levels of Human Immunodeficiency Virus DNA Are Determined Before ART Initiation and Linked to CD8 T-Cell Activation and Memory Expansion
    Martin, Genevieve E.
    Pace, Matthew
    Shearer, Freya M.
    Zilber, Eva
    Hurst, Jacob
    Meyerowitz, Jodi
    Thornhill, John P.
    Lwanga, Julianne
    Brown, Helen
    Robinson, Nicola
    Hopkins, Emily
    Olejniczak, Natalia
    Nwokolo, Nneka
    Fox, Julie
    Fidler, Sarah
    Willberg, Christian B.
    Frater, John
    JOURNAL OF INFECTIOUS DISEASES, 2020, 221 (07) : 1135 - 1145
  • [8] CD4+FOXP3+regulatory T-cell subsets in human immunodeficiency virus infection
    Simonetta, Federico
    Bourgeois, Christine
    FRONTIERS IN IMMUNOLOGY, 2013, 4
  • [9] The impact of viral evolution and frequency of variant epitopes on primary and memory human immunodeficiency virus type 1-specific CD8+ T cell responses
    Melhem, Nada M.
    Smith, Kellie N.
    Huang, Xiao-Li
    Colleton, Bonnie A.
    Jiang, Weimin
    Mailliard, Robbie B.
    Mullins, James I.
    Rinaldo, Charles R.
    VIROLOGY, 2014, 450 : 34 - 48
  • [10] CD8+ T-cell Cytotoxic Capacity Associated with Human Immunodeficiency Virus-1 Control Can Be Mediated through Various Epitopes and Human Leukocyte Antigen Types
    Migueles, Stephen A.
    Mendoza, Daniel
    Zimmerman, Matthew G.
    Martins, Kelly M.
    Toulmin, Sushila A.
    Kelly, Elizabeth P.
    Peterson, Bennett A.
    Johnson, Sarah A.
    Galson, Eric
    Poropatich, Kate O.
    Patamawenu, Andy
    Imamichi, Hiromi
    Ober, Alexander
    Rehm, Catherine A.
    Jones, Sara
    Hallahan, Claire W.
    Follmann, Dean A.
    Connors, Mark
    EBIOMEDICINE, 2015, 2 (01): : 46 - 58