Longitudinal changes in CD4+ T cell antigen receptor diversity and naive/memory cell phenotype during 9 to 26 months of antiretroviral therapy of HIV-infected patients.
Although skewing of the CD4+ TCR repertoire in advanced HIV infection is well documented, increases in polyclonality during antiretroviral therapy have been less consistently observed. Ten patients, each with documented abnormalities within the CD4+ TCR repertoire, were studied by CDR3 spectratyping, semiquantitative PCR, and SSCP during 9-26 months of therapy. Naive and memory cell phenotypes were analyzed by flow cytometry. Six of 10 patients showed increased polyclonality of their TCR repertoires, 1 showed no change, and 3 showed increased TCR skewing, despite suppressed viral replication. Overall, there was no significant change in the percentage of abnormal BV subfamilies (from a mean of 25.5 to 17.1%) or the percentage of naive CD4+ T cells (from a mean of 18 to 25%). Further, progression of TCR repertoire disruptions was observed in some patients even with suppression of plasma viral RNA below 500 copies/ml. Although a spectrum of changes may be seen within the CD4+ TCR repertoire in the setting of antiretroviral therapy, increases in polyclonality are observed in some patients.
Gea-Banacloche
J C
JC
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Martino
L
L
Mican
J M
JM
Hallahan
C W
CW
Baseler
M
M
Stevens
R
R
Lambert
L
L
Polis
M
M
Lane
H C
HC
Connors
M
M
D019380:Anti-HIV Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000145:classification / Q000276:immunology* / Q000378:metabolism; D022801:Complementarity Determining Regions / Q000378:metabolism; D004359:Drug Therapy, Combination; D005434:Flow Cytometry; D014644:Genetic Variation / Q000235:genetics; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory; D010641:Phenotype; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011446:Prospective Studies; D011948:Receptors, Antigen, T-Cell / Q000235:genetics* / Q000378:metabolism; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D014158:Transcription, Genetic; D014779:Virus Replication
D019380:Anti-HIV Agents; D022801:Complementarity Determining Regions; D011948:Receptors, Antigen, T-Cell; D018894:Reverse Transcriptase Inhibitors