In vivo expansion of CD4CD45RO-CD25 T cells expressing foxP3 in IL-2-treated HIV-infected patients.
Administration of IL-2 to HIV-infected patients leads to expansion of a unique subset of CD4CD45ROCD25 cells. In this study, the origin, clonality, and function of these cells were investigated. Analysis of TCR excision circles revealed that the CD4CD45ROCD25 cells were the product of peripheral expansion but remained polyclonal as determined by TCR repertoire analysis. Phenotypically, these cells were distinct from naturally occurring Tregs; they exhibited intermediate features, between those of memory and naive cells, and had lower susceptibility to apoptosis than CD45ROCD25 or memory T cells. Studies of intracellular cytokine production and proliferation revealed that cytokine-expanded naive CD25 cells had low IL-2 production and required costimulation for proliferation. Despite elevated expression of forkhead transcription factor P3 (foxP3), they exerted only weak suppression compared with CD45ROCD25 cells (Tregs). In summary, in vivo IL-2 administration to HIV-infected patients leads to peripheral expansion of a population of long-lived CD4CD45ROCD25 cells that express high levels of foxP3 but exert weak suppressive function. These CD4CD25 cytokine-expanded naive cells, distinct from antigen-triggered cells and Tregs, play a role in the maintenance of a state of low turnover and sustained expansion of the CD4 T cell pool.
Sereti
Irini
I
National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA. isereti@niaid.nih.gov
Imamichi
Hiromi
H
Natarajan
Ven
V
Imamichi
Tomozumi
T
Ramchandani
Meena S
MS
Badralmaa
Yunden
Y
Berg
Steve C
SC
Metcalf
Julia A
JA
Hahn
Barbara K
BK
Shen
Jean M
JM
Powers
April
A
Davey
Richard T
RT
Kovacs
Joseph A
JA
Shevach
Ethan M
EM
Lane
H Clifford
HC
D000328:Adult; D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D049109:Cell Proliferation; D015331:Cohort Studies; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005500:Follow-Up Studies; D051858:Forkhead Transcription Factors; D015870:Gene Expression; D015658:HIV Infections / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007156:Immunologic Memory; D007376:Interleukin-2 / Q000627:therapeutic use*; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008875:Middle Aged; D010641:Phenotype; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D011994:Recombinant Proteins / Q000627:therapeutic use; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000473:pathology
D004268:DNA-Binding Proteins; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins; D017493:Leukocyte Common Antigens