Decreased CD95 expression on naive T cells from HIV-infected persons undergoing highly active anti-retroviral therapy (HAART) and the influence of IL-2 low dose administration

A. Amendola, F. Poccia, F. Martini, C. Gioia, V. Galati, M. Pierdominici, M. Marziali, F. Pandolfi, V. Colizzi, M. Piacentini, E. Girardi, Gianpiero D'Offizi

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

The functional recovery of the immune system in HIV-infected persons receiving HAART and the role of adjuvant immune therapy are still matters of intensive investigation. We analysed the effects of HAART combined with cytokines in 22 naive asymptomatic individuals, randomized to receive HAART (n = 6), HAART plus a low dose (1000 000 U/daily) of rIL-2 (n = 8), and HAART plus rIL-2 after previous administration of granulocyte colony-stimulating factor (n = 8). After 3 months of therapy, increased CD4+ T cell counts and diminished viral loads were observed in all patients, independently of cytokine addition. A decreased expression of CD95 (Apo l/Fas) was evident in all groups when compared with values before therapy. The percentages of peripheral blood mononuclear cells (PBMC) expressing CD95 after therapy decreased by 15%, 22% and 18% in the three treatment groups, respectively (P <0.05). Analysis of PBMC subsets demonstrated that CD95 expression was significantly reduced on CD45RA+ CD62L+ naive T cells (25.3%, 22.4%, and 18.6%, respectively; P <0.05) in each group, after therapy. Accordingly, all patients showed a reduced rate of in vitro spontaneous apoptosis (P <0.05). Another effect induced by HAART was a significant increase in IL2Rα expression on total PBMC (P <0.05), independently of cytokine addition. Altogether, our results suggest that very low dose administration of rIL-2 (1000 000 U/daily) may be not enough to induce a significant improvement in the immune system as regards HAART alone. The employment of higher doses of recombinant cytokines and/or different administration protocols in clinical trials might however contribute to ameliorate the immune reconstitution in patients undergoing HAART.

Original languageEnglish
Pages (from-to)324-332
Number of pages9
JournalClinical and Experimental Immunology
Volume120
Issue number2
DOIs
Publication statusPublished - 2000

Fingerprint

Interleukin-2
HIV
T-Lymphocytes
Therapeutics
Cytokines
Blood Cells
Immune System
Granulocyte Colony-Stimulating Factor
CD4 Lymphocyte Count
Group Psychotherapy
Viral Load
Clinical Trials
Apoptosis

Keywords

  • Apoptosis
  • CD95
  • HAART
  • IL-2
  • Naive cells

ASJC Scopus subject areas

  • Immunology

Cite this

@article{064c0e3fadb342829cd68d481c8dcfa7,
title = "Decreased CD95 expression on naive T cells from HIV-infected persons undergoing highly active anti-retroviral therapy (HAART) and the influence of IL-2 low dose administration",
abstract = "The functional recovery of the immune system in HIV-infected persons receiving HAART and the role of adjuvant immune therapy are still matters of intensive investigation. We analysed the effects of HAART combined with cytokines in 22 naive asymptomatic individuals, randomized to receive HAART (n = 6), HAART plus a low dose (1000 000 U/daily) of rIL-2 (n = 8), and HAART plus rIL-2 after previous administration of granulocyte colony-stimulating factor (n = 8). After 3 months of therapy, increased CD4+ T cell counts and diminished viral loads were observed in all patients, independently of cytokine addition. A decreased expression of CD95 (Apo l/Fas) was evident in all groups when compared with values before therapy. The percentages of peripheral blood mononuclear cells (PBMC) expressing CD95 after therapy decreased by 15{\%}, 22{\%} and 18{\%} in the three treatment groups, respectively (P <0.05). Analysis of PBMC subsets demonstrated that CD95 expression was significantly reduced on CD45RA+ CD62L+ naive T cells (25.3{\%}, 22.4{\%}, and 18.6{\%}, respectively; P <0.05) in each group, after therapy. Accordingly, all patients showed a reduced rate of in vitro spontaneous apoptosis (P <0.05). Another effect induced by HAART was a significant increase in IL2Rα expression on total PBMC (P <0.05), independently of cytokine addition. Altogether, our results suggest that very low dose administration of rIL-2 (1000 000 U/daily) may be not enough to induce a significant improvement in the immune system as regards HAART alone. The employment of higher doses of recombinant cytokines and/or different administration protocols in clinical trials might however contribute to ameliorate the immune reconstitution in patients undergoing HAART.",
keywords = "Apoptosis, CD95, HAART, IL-2, Naive cells",
author = "A. Amendola and F. Poccia and F. Martini and C. Gioia and V. Galati and M. Pierdominici and M. Marziali and F. Pandolfi and V. Colizzi and M. Piacentini and E. Girardi and Gianpiero D'Offizi",
year = "2000",
doi = "10.1046/j.1365-2249.2000.01223.x",
language = "English",
volume = "120",
pages = "324--332",
journal = "Clinical and Experimental Immunology",
issn = "0009-9104",
publisher = "Wiley-Blackwell",
number = "2",

}

TY - JOUR

T1 - Decreased CD95 expression on naive T cells from HIV-infected persons undergoing highly active anti-retroviral therapy (HAART) and the influence of IL-2 low dose administration

AU - Amendola, A.

AU - Poccia, F.

AU - Martini, F.

AU - Gioia, C.

AU - Galati, V.

AU - Pierdominici, M.

AU - Marziali, M.

AU - Pandolfi, F.

AU - Colizzi, V.

AU - Piacentini, M.

AU - Girardi, E.

AU - D'Offizi, Gianpiero

PY - 2000

Y1 - 2000

N2 - The functional recovery of the immune system in HIV-infected persons receiving HAART and the role of adjuvant immune therapy are still matters of intensive investigation. We analysed the effects of HAART combined with cytokines in 22 naive asymptomatic individuals, randomized to receive HAART (n = 6), HAART plus a low dose (1000 000 U/daily) of rIL-2 (n = 8), and HAART plus rIL-2 after previous administration of granulocyte colony-stimulating factor (n = 8). After 3 months of therapy, increased CD4+ T cell counts and diminished viral loads were observed in all patients, independently of cytokine addition. A decreased expression of CD95 (Apo l/Fas) was evident in all groups when compared with values before therapy. The percentages of peripheral blood mononuclear cells (PBMC) expressing CD95 after therapy decreased by 15%, 22% and 18% in the three treatment groups, respectively (P <0.05). Analysis of PBMC subsets demonstrated that CD95 expression was significantly reduced on CD45RA+ CD62L+ naive T cells (25.3%, 22.4%, and 18.6%, respectively; P <0.05) in each group, after therapy. Accordingly, all patients showed a reduced rate of in vitro spontaneous apoptosis (P <0.05). Another effect induced by HAART was a significant increase in IL2Rα expression on total PBMC (P <0.05), independently of cytokine addition. Altogether, our results suggest that very low dose administration of rIL-2 (1000 000 U/daily) may be not enough to induce a significant improvement in the immune system as regards HAART alone. The employment of higher doses of recombinant cytokines and/or different administration protocols in clinical trials might however contribute to ameliorate the immune reconstitution in patients undergoing HAART.

AB - The functional recovery of the immune system in HIV-infected persons receiving HAART and the role of adjuvant immune therapy are still matters of intensive investigation. We analysed the effects of HAART combined with cytokines in 22 naive asymptomatic individuals, randomized to receive HAART (n = 6), HAART plus a low dose (1000 000 U/daily) of rIL-2 (n = 8), and HAART plus rIL-2 after previous administration of granulocyte colony-stimulating factor (n = 8). After 3 months of therapy, increased CD4+ T cell counts and diminished viral loads were observed in all patients, independently of cytokine addition. A decreased expression of CD95 (Apo l/Fas) was evident in all groups when compared with values before therapy. The percentages of peripheral blood mononuclear cells (PBMC) expressing CD95 after therapy decreased by 15%, 22% and 18% in the three treatment groups, respectively (P <0.05). Analysis of PBMC subsets demonstrated that CD95 expression was significantly reduced on CD45RA+ CD62L+ naive T cells (25.3%, 22.4%, and 18.6%, respectively; P <0.05) in each group, after therapy. Accordingly, all patients showed a reduced rate of in vitro spontaneous apoptosis (P <0.05). Another effect induced by HAART was a significant increase in IL2Rα expression on total PBMC (P <0.05), independently of cytokine addition. Altogether, our results suggest that very low dose administration of rIL-2 (1000 000 U/daily) may be not enough to induce a significant improvement in the immune system as regards HAART alone. The employment of higher doses of recombinant cytokines and/or different administration protocols in clinical trials might however contribute to ameliorate the immune reconstitution in patients undergoing HAART.

KW - Apoptosis

KW - CD95

KW - HAART

KW - IL-2

KW - Naive cells

UR - http://www.scopus.com/inward/record.url?scp=0034125406&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034125406&partnerID=8YFLogxK

U2 - 10.1046/j.1365-2249.2000.01223.x

DO - 10.1046/j.1365-2249.2000.01223.x

M3 - Article

VL - 120

SP - 324

EP - 332

JO - Clinical and Experimental Immunology

JF - Clinical and Experimental Immunology

SN - 0009-9104

IS - 2

ER -