Molecular tracking of an Human Immunodeficiency Virus nef specific cytotoxic T-cell clone shows persistence of clone-specific T-cell receptor DNA but not mRNA following early combination antiretroviral therapy.
The mechanisms that lead to maintenance of an active effector cytotoxic T-cell (CTL) response in Human Immunodeficiency Virus type-1 (HIV-1) infection are not well understood. We have investigated the role of antigen in maintenance of an HIV-1 specific CTL response by studying a patient (313-7) whose antigenic stimulus was reduced using antiretroviral drug therapy started within 90 days of HIV-1 infection. This patient made a primary monospecific CTL response to an HLA-C*0802 restricted epitope in nef (KAAVDLSHFL) prior to treatment. Within 7 days of starting treatment the nef specific CTL precursor frequency (CTLp) had decreased from 60/10(6) to 4/10(6) peripheral blood mononuclear cells (PBMC), coincident with a decline in viremia from 18 470 to 615 copies/ml. Both plasma viremia and nef specific CTLp remained at low levels for 180 days. The nef-specific CTL clone T-cell receptor (TCR) mRNA transcripts also decreased after treatment, but clone specific TCR DNA persisted. It appears that removal of antigen alters the state of HIV specific CTL from an activated effector population (detected in the CTLp assay and by measurement of clone specific RNA) to a non-activated quiescent population (detected by measurement of clone-specific DNA). This latter population may represent persisting HIV specific memory CTL.
Nixon
D F
DF
Aaron Diamond AIDS Research Center, The Rockefeller University, New York, NY 10016, USA. dnixon@adarc.org
Douek
D
D
Kuebler
P J
PJ
Jin
X
X
Vesanen
M
M
Bonhoeffer
S
S
Cao
Y
Y
Koup
R A
RA
Ho
D D
DD
Markowitz
M
M
D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D004247:DNA; D004359:Drug Therapy, Combination; D015693:Gene Products, nef / Q000276:immunology*; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007700:Kinetics; D008297:Male; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D054311:nef Gene Products, Human Immunodeficiency Virus
D019380:Anti-HIV Agents; D015693:Gene Products, nef; D017320:HIV Protease Inhibitors; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D018894:Reverse Transcriptase Inhibitors; D054311:nef Gene Products, Human Immunodeficiency Virus; D004247:DNA