Frequency of cytokine-producing T cells in HIV-infected patients treated with stavudine, didanosine, and ritonavir.
To assess prospectively the influence of the control of viral replication on the frequency of cytokine-producing T cells, and to correlate these changes with immune activation, we conducted a 15-month follow-up study of IFN-gamma- and IL-2-producing CD4+ and CD8+ T cells at a single-cell level in 12 previously untreated patients receiving highly active antiretroviral therapy (HAART). At baseline we observed a strikingly high proportion of IFN-gamma-producing CD8+ T cells. The treatment-induced decrease in the proportion of IFN-gamma-producing CD8+ T cells ran parallel to the decrease in HLA-DR+ and CD38+CD8+ T cell subsets and was associated with the reduction in HIV RNA level. IL-2-producing cells were mainly CD4+. As a consequence of CD4+ T cell loss, the number of IL-2-producing CD4+ T cells was lower in patients than in control subjects (52 vs. 171 cells/microl), but the proportion of these cells was unchanged (22.4 vs. 19.3). During therapy the proportion of CD4+ IL-2-producing cells was initially stable and then fell markedly at month 5, followed by a gradual return to previous values. The reduction in viral load was associated with the fall in the proportion of CD4+ activated subsets. Intracellular cytokine assays are a new approach to the assessment of T cell function in HIV infection. Our results suggest that the functional capacity of CD4+ T cells is probably less severely altered than previously thought on the basis of conventional assays. CD8+ T cells exhibit an increased capacity to produce IFN-gamma that is associated with an increase in activation marker expression. These alterations decrease partially and in parallel under treatment.
Levacher
M
M
Institut National de la Santé et de la Recherche Médicale Unité, Paris, France.
Bouscarat
F
F
Landman
R
R
Chau
F
F
Damond
F
F
Gaudebout
C
C
Mathez
D
D
Leibowitch
J
J
Saimot
A G
AG
Sinet
M
M
D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis*; D016049:Didanosine / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D008297:Male; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D019438:Ritonavir / Q000627:therapeutic use; D018119:Stavudine / Q000627:therapeutic use; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D019562:Viral Load
D019380:Anti-HIV Agents; D016207:Cytokines; D007376:Interleukin-2; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D007371:Interferon-gamma; D018119:Stavudine; D016049:Didanosine; D019438:Ritonavir