AEGiS-04CROI: Dynamics of the CD4 T helper cell subset reconstitution after combined anti-retroviral therapies.

4th Conference on Retroviruses and Opportunistic Infections


Washington, DC - January 22-26, 1997

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Dynamics of the CD4 T helper cell subset reconstitution after combined anti-retroviral therapies.

Conf Retroviruses Opportunistic Infect 1997 Jan 22-26; 4th:71 (abstract no. 34)

Autran B, Mathez D, Carcelain G, Blanc C, Debre P, Leibowitch J; Lab. Cellul. Immunol., Hop. Pitie-Salpetriere, Paris, France.

Aim of the study: to evaluate the sequential events of CD4+ T cell subset reconstitution after anti-retroviral therapies (ART) with 1 protease-inhibitor and 2 nucleoside analogs. The nature and the mechanism of CD4 amplification after potent ART remains unknown and has major implications for treatment of the HIV-induced immune efficiency.

Methods: 20 naïve patients [mean CD4:170/ml plus or minus 73, viral load:4.6log10 RNA copies/ml]) started a treament with Ritonavir and AZT+ddC in March 1995. Lymphoid subsets (T:CD3, CD4, CD8, B:CD19, NK: CD16+56+) were evaluated on frozen PBL from 8 representative donors by 4 color-flow-cytometry using anti-CD45RA/RO, CD62L, 25, 38, 57, 69, HLA-DR (Coulter), combined to CD7, CD28.

Results: A mean 3 log viral load decrease and 60% increase in absolute CD4+ counts was observed at day 15 and sustained afterward. At day 15 the PBL increase predominated on CD4 cells (+20%) as compared to CD8 (+12%), B or NK cells (-15%), with a peak of activated memory (CD45RO+RA-, CD25+) cells at day 15 (+35%) but without CD69+ or proliferating cells. This was followed at month 4-6 by a significant decrease in activation (CD25:-30%, CD38:-50%, DR:-50%), CD4+28+cell increase (+25%) and a late (M6) increase of naïve CD4+CD45RA+62L+cells (+30%) in 4/8 patients only.

Conclusions: Combined ART decrease HIV replication and allow mobilization of activated memory CD4+ cells from the mature T cell pool, followed by T cell de-activation and, in some cases, by a late increase of naïve CD4+ cells. Long-term follow-up will help to analyze whether the persisting ART-mediated low viral replication and antigen stimulation might lately allow de-novo T cell differentiation or rather limit conversion from naïve to memory cells and consumption of the naïve CD4+ cell pool. These findings should help to define stategies for immune reconstitution and immune responders to anti-retroviral therapies.

Keywords: AEGIS, Antigens, CD4, T-Lymphocytes, Helper-Inducer, Zidovudine, CD4 Lymphocyte Count, T-Lymphocyte Subsets, Viral Load, Antigens, CD8, Antigens, CD45, Anti-HIV Agents, T-Lymphocytes, Antigens, CD, Antigens, Differentiation, Reverse Transcriptase Inhibitors, Flow Cytometry, Leu-23 antigen, T10 antigen, Human, AIDS

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Copyright © 1980, 1997 - Foundation for Retrovirology and Human Health. Reproduction of this abstract (other than one copy for personal reference) must be cleared through the Foundation for Retrovirology and Human Health. Licensed through AIDSLINE, National Library of Medicine.