CD4+ and CD8+ T cells expressing FoxP3 in HIV-infected patients are phenotypically distinct and influenced by disease severity and antiretroviral therapy.
OBJECTIVE
Forkhead box P3 (FoxP3) is critical for the development of CD4 regulatory T (Treg) cells and is a useful marker to identify this population. Recently, expression of FoxP3 was reported in human CD8 T cells from the blood of untreated HIV-infected individuals. We assessed whether FoxP3 expression in CD8 T cells is associated with suppressive potential and/or with HIV-associated immune activation.


METHODS
FoxP3CD8 T cells in non-HIV donors and in untreated and treated HIV-infected patients were identified by flow cytometry, then examined for coexpression of other Treg cell-associated markers [cytotoxic T lymphocyte-associated antigen (CTLA)-4, GITR, and CD45RO], markers of activation [HLA-DR, Ki-67, and programmed death (PD)-1], and markers of senescence (CD57 without CD28).


RESULTS
Similar proportions of FoxP3-expressing CD4 and CD8 T cells coexpressed HLA-DR and Ki-67. However, compared with FoxP3CD4 cells, FoxP3CD8 cells expressed less CTLA-4, CD28, and CD45RO but more PD-1 and CD57. FoxP3-expressing CD4 and CD8 cells from untreated patients exhibited higher expression of HLA-DR, Ki-67, and PD-1 compared with non-HIV donors and treated patients.


CONCLUSIONS
FoxP3CD8 T cells are phenotypically distinct from FoxP3CD4 and FoxP3CD8 T cells. Expression of FoxP3 is associated with cellular activation in both CD4 and CD8 T cells.
School of Pathology and Laboratory Medicine, University of Western Australia, Nedlands, Perth, Western Australia 6000, Australia. andrew.lim@uwa.edu.au
Andrew
A
Lim
Martyn A
MA
French
Patricia
P
Price
D000328:Adult; D015703:Antigens, CD / Q000378:metabolism; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D018106:CD28 Antigens / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000821:virology; D018959:CD57 Antigens / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D060908:CTLA-4 Antigen; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D053450:Glucocorticoid-Induced TNFR-Related Protein; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008213:Lymphocyte Activation / Q000502:physiology; D008297:Male; D008875:Middle Aged; D061026:Programmed Cell Death 1 Receptor; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism / Q000821:virology
D015703:Antigens, CD; D051017:Apoptosis Regulatory Proteins; D018106:CD28 Antigens; D018959:CD57 Antigens; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053450:Glucocorticoid-Induced TNFR-Related Protein; D006684:HLA-DR Antigens; D019394:Ki-67 Antigen; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D017475:Receptors, Nerve Growth Factor; D018124:Receptors, Tumor Necrosis Factor; C491405:TNFRSF18 protein, human; D017493:Leukocyte Common Antigens