The CD8+ HLA-DR+ T cells expanded in HIV-1 infection are qualitatively identical to those from healthy controls.
HIV-induced immune activation leads to expansion of a subset of human CD8(+)  T cells expressing HLA-DR antigens. Expansion of CD8(+) HLA-DR(+)  T cells can be also observed in non-HIV settings including several autoimmune diseases and aging. Although these cells are felt to represent "immune exhaustion" and/or to be anergic, their precise role in host defense has remained unclear. Here, we report that this subset of cells exhibits a restricted repertoire, shows evidence of multiple rounds of division, but lacks markers of recent TCR engagement. Detailed cell cycle analysis revealed that compared with their CD8(+) HLA-DR(-)  counterpart, the CD8(+) HLA-DR(+)  T-cell pool contained an increased fraction of cells in S-phase with elevated levels of the G2/M regulators: cyclin A2, CDC25C, Cdc2 (CDK1), indicating that these cells are not truly anergic but rather experiencing proliferation in vivo. Together, these data support a hypothesis that antigen stimulation leads to the initial expansion of a CD8(+)  pool of cells in vivo that undergo further expansion independent of ongoing TCR engagement. No qualitative differences were noted between CD8(+) HLA-DR(+)  cells from HIV(+)  and HIV(-)  donors, indicating that the generation of CD8(+) HLA-DR(+)  T cells is a part of normal immune regulation that is exaggerated in the setting of HIV-1 infection.
Clinical and Molecular Retrovirology Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. himamichi@nih.gov
Hiromi
H
Imamichi
Richard A
RA
Lempicki
Joseph W
JW
Adelsberger
Rebecca B
RB
Hasley
Alice
A
Rosenberg
Gregg
G
Roby
Catherine A
CA
Rehm
Amy
A
Nelson
Sonya
S
Krishnan
Mark
M
Pavlick
Christian J
CJ
Woods
Michael W
MW
Baseler
H Clifford
HC
Lane
D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D017635:Clonal Anergy; D005786:Gene Expression Regulation / Q000276:immunology; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006684:HLA-DR Antigens / Q000378:metabolism*; D006801:Humans; D008213:Lymphocyte Activation; D008875:Middle Aged; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000821:virology
D015415:Biomarkers; D018797:Cell Cycle Proteins; D006684:HLA-DR Antigens; D011948:Receptors, Antigen, T-Cell