T cell responses to highly active antiretroviral therapy defined by chemokine receptors expression, cytokine production, T cell receptor repertoire and anti-HIV T-lymphocyte activity.
The immunological correlates of highly active antiretroviral therapy (HAART)-induced suppression of human immunodeficiency virus type 1 (HIV-1) replication have been investigated. 20 HIV-1-infected patients with mean CD4+ T cell count of 298/microl, plasma viral load of 4.7 log10 copies/ml and naive for protease inhibitors (PI) were studied during12 months of HAART. An increased number of both CD4+ and CD8+ naive T cells and a normalization of the frequency of CCR5- and CXCR4-expressing CD4+ T cells were readily observed after starting therapy. Single cell analysis of cytokine production after 12 months of HAART showed an increased number of interleukin (IL)-2-, but not IL-4- and (IFN)-gamma-, producing T cells and a decreased percentage of CD8+ IFN-gamma + cells. A correlation between the frequency of IFN-gamma-producing T cells and that of memory, CCR5+ and CD95+ T cells was demonstrated in both CD4+ and CD8+ subsets. The diversity of T cell receptor (TCR) variable beta (BV) chain repertoire significantly increased after 12 months of HAART within the CD4+ but not the CD8+ T cell subset. However, the level of perturbation of the third complementarity-determining region (CDR3), was not significantly modified by effective therapy. The number of anti-HIV Gag and Pol cytotoxic T lymphocytes precursors (CTLp) decreased during HAART and highly correlated with the CD8 IFN-gamma response. Ameliorated clinical conditions were observed in all patients in absence of any opportunistic infections during all the study period. These observations indicate that a better restoration of immunity may be obtained in patients starting HAART at less advanced stages of the disease.
Giovannetti
A
A
Department of Clinical Medicine, Division of Clinical Immunology and Allergy, University of Rome 'La Sapienza', Italy. antonello.giovannetti@uniroma1.it
Pierdominici
M
M
Mazzetta
F
F
Salemi
S
S
Marziali
M
M
Kuonen
D
D
Iebba
F
F
Lusi
E A
EA
Cossarizza
A
A
Aiuti
F
F
D000328:Adult; D000956:Antigens, Viral / Q000276:immunology; D023241:Antiretroviral Therapy, Highly Active; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D015683:Gene Products, gag / Q000276:immunology; D015684:Gene Products, pol / Q000276:immunology; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology* / Q000502:physiology; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D019707:Receptors, Chemokine / Q000096:biosynthesis*; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology; D019562:Viral Load; D014779:Virus Replication / Q000187:drug effects
D000956:Antigens, Viral; D016207:Cytokines; D015683:Gene Products, gag; D015684:Gene Products, pol; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; D019707:Receptors, Chemokine; D015847:Interleukin-4