Features of 'CD4-exploders', HIV-positive patients with an optimal immune reconstitution after potent antiretroviral therapy.
OBJECTIVE
To identify crucial immunological characteristics of a group of patients, defined 'CD4-exploders', who were able to fully reconstitute their immune system after receiving highly active antiretroviral therapy (HAART).


METHODS
Among a population of 540 HIV-positive patients treated with HAART, six individuals were identified who experienced a nadir of less than 85 x 106 CD4+ cells/l, had major opportunistic infections (four out of six), started HAART in 1996 or 1997, and showed a rapid and relevant CD4+ lymphocyte increase (mainly due to virgin cells), in some cases regardless of virological control.


METHODS
Enzyme-linked immunosorbent assay for the determination of interleukin (IL)-7 plasma levels; flow cytometry to analyse surface antigens and CD127 (IL-7 receptor alpha-chain) expression; quantitative-competitive (QC) PCR for detecting cells containing T-cell receptor rearrangement excision circles (TREC); chest-computed tomography (CT) to analyse thymus volume and content.


RESULTS
In 'CD4-exploders', high levels of TREC+ lymphocytes were found among CD4+ T cells, which also contained a high percentage of naive cells. However, CT revealed a dramatic depletion of intrathymic lymphoid tissue. Plasma levels of IL-7 were significantly high. Most CD4+ and CD8+ T lymphocytes expressed CD127, whose level was similar to that of healthy donors. CD127 expression on CD8+ lymphocytes was markedly higher than in HIV-positive individuals treated with the same therapy or in patients with AIDS.


CONCLUSIONS
In 'CD4-exploders', HAART-induced reconstitution of the T-cell compartment is independent from thymus volume, and is favoured by the upregulation of the IL-7/IL-7 receptor system.
Mussini
Cristina
C
Infectious Diseases Clinic, University of Modena and Reggio Emilia School of Medicine and Azienda Ospedaliera Policlinico Modena, Modena, Italy.
Pinti
Marcello
M
Borghi
Vanni
V
Nasi
Milena
M
Amorico
Grazia
G
Monterastelli
Elena
E
Moretti
Laura
L
Troiano
Leonarda
L
Esposito
Roberto
R
Cossarizza
Andrea
A
D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D002455:Cell Division; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D015851:Interleukin-7 / Q000097:blood; D008221:Lymphoid Tissue / Q000000981:diagnostic imaging; D010641:Phenotype; D016133:Polymerase Chain Reaction; D020395:Receptors, Interleukin-7 / Q000097:blood; D013950:Thymus Gland / Q000000981:diagnostic imaging; D014057:Tomography, X-Ray Computed
D015851:Interleukin-7; D020395:Receptors, Interleukin-7