High frequency and proliferation of CD4+ FOXP3+ Treg in HIV-1-infected patients with low CD4 counts. 2009

Xiuqiong Bi, and Yasuhiro Suzuki, and Hiroyuki Gatanaga, and Shinichi Oka
AIDS Clinical Center, International Medical Center of Japan, Tokyo, Japan.

The frequency of Treg is reported to be higher in patients with chronic HIV type 1 (HIV-1) infection and CD45RA(+) Treg exist in normal adults. In this study, we found a lower absolute number (15 cells/microL) but a higher proportion (16.2%) of FOXP3(+) cells (Treg) in the CD4(+) population in treatment-naïve HIV-1 patients with low CD4 (<200 cells/microL) counts than in those with high CD4 counts (34 cells/microL and 9.3%) or healthy adults (48 cells/microL and 7.5%). In HIV-1 patients, CD45RA(+)CCR7(+), CD45RA(-)CCR7(+), and CD45RA(-)CCR7(-) subsets were identified in the Treg population, and the proportion of CD45RA(-)CCR7(-) Treg was higher (57.9%) in patients with low CD4 than high CD4 counts (38.3%). Treg were in a high proliferation state especially in patients with low CD4 counts. HIV viral load correlated positively with the Treg proliferation rate and the proportion of CD45RA(-)CCR7(-) Treg. Furthermore, the proliferation of Treg correlated positively with the CD45RA(-)CCR7(-) Treg proportion but negatively with Treg numbers. Successful antiretroviral therapy resulted in a limited increase in Treg numbers, but their frequency was reduced in 1-2 months due to a rapid rebound of FOXP3(-) CD4(+)cells. Our results suggest that HIV-activating Treg may be a reason for the high frequencies of Treg and CD45RA(-)CCR7(-) Treg in the peripheral blood of late-stage HIV-1-infected patients.

UI MeSH Term Description Entries
D008297 Male Males
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000328 Adult A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available. Adults
D000368 Aged A person 65 years of age or older. For a person older than 79 years, AGED, 80 AND OVER is available. Elderly
D015497 HIV-1 The type species of LENTIVIRUS and the etiologic agent of AIDS. It is characterized by its cytopathic effect and affinity for the T4-lymphocyte. Human immunodeficiency virus 1,HIV-I,Human Immunodeficiency Virus Type 1,Immunodeficiency Virus Type 1, Human
D015658 HIV Infections Includes the spectrum of human immunodeficiency virus infections that range from asymptomatic seropositivity, thru AIDS-related complex (ARC), to acquired immunodeficiency syndrome (AIDS). HTLV-III Infections,HTLV-III-LAV Infections,T-Lymphotropic Virus Type III Infections, Human,HIV Coinfection,Coinfection, HIV,Coinfections, HIV,HIV Coinfections,HIV Infection,HTLV III Infections,HTLV III LAV Infections,HTLV-III Infection,HTLV-III-LAV Infection,Infection, HIV,Infection, HTLV-III,Infection, HTLV-III-LAV,Infections, HIV,Infections, HTLV-III,Infections, HTLV-III-LAV,T Lymphotropic Virus Type III Infections, Human
D015704 CD4 Antigens 55-kDa antigens found on HELPER-INDUCER T-LYMPHOCYTES and on a variety of other immune cell types. They are members of the immunoglobulin supergene family and are implicated as associative recognition elements in MAJOR HISTOCOMPATIBILITY COMPLEX class II-restricted immune responses. On T-lymphocytes they define the helper/inducer subset. T4 antigens also serve as INTERLEUKIN-15 receptors and bind to the HIV receptors, binding directly to the HIV ENVELOPE PROTEIN GP120. Antigens, CD4,CD4 Molecule,CD4 Receptor,CD4 Receptors,Receptors, CD4,T4 Antigens, T-Cell,CD4 Antigen,Receptors, Surface CD4,Surface CD4 Receptor,Antigen, CD4,Antigens, T-Cell T4,CD4 Receptor, Surface,CD4 Receptors, Surface,Receptor, CD4,Surface CD4 Receptors,T-Cell T4 Antigens,T4 Antigens, T Cell
D049109 Cell Proliferation All of the processes involved in increasing CELL NUMBER including CELL DIVISION. Cell Growth in Number,Cellular Proliferation,Cell Multiplication,Cell Number Growth,Growth, Cell Number,Multiplication, Cell,Number Growth, Cell,Proliferation, Cell,Proliferation, Cellular

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