Differential disappearance of inhibitory natural killer cell receptors during HAART and possible impairment of HIV-1-specific CD8 cytotoxic T lymphocytes

Paola Costa, Stefano Rusconi, Domenico Mavilio, Manuela Fogli, Giuseppe Murdaca, Daniela Pende, Maria Cristina Mingari, Massimo Galli, Lorenzo Moretta, Andrea De Maria

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Background: Highly active antiretroviral therapy (HAART) is associated with a decrease in viral replication to undetectable levels and with an increase in CD4 T lymphocytes. Residual HIV-1 replication occurs together with incomplete recovery of cytotoxic CD8 T lymphocyte (CTL) numbers and function. We sought to determine whether expression of HLA class I-specific inhibitory natural killer receptors (iNKR) on the CTL of patients who had been treated successfully with HAART for 24 months could be involved, at least in part, in residual CTL functional inhibition. Methods: Two-colour cytofluorometry was used to analyse the expression of six different iNKR including p58.1, p58.2, p70, p140, CD94/NKG2A and LIR1/ILT2 on the CD3, CD8 lymphocytes of eight patients with successful long-term suppression of viral replication before and after 3, 6 and 24 months of HAART. Healthy subjects were analysed as controls. HIV-1 -specific cytotoxic activity was determined after 24 months of HAART in the presence and absence of iNKR-masking. Results: No significant reduction of iNKR expression on CD8 T cells was observed by 6 months. Expression of p70 and p140 was inversely correlated with the increasing CD4 numbers. After 24 months CD8 T-lymphocytes expressing p58.1, p58.2, p70, p140 and CD94/NKG2A returned to levels indistinguishable from those of the healthy controls. A significantly increased proportion of CD8 CTL still expressed LIR1/ILT2, a receptor with broad HLA-class I specificity. Functional analysis of freshly separated cells revealed that the disruption of the interaction between LIR1/ILT2 and HLA-class I could partly restore HIV-1-specific lysis. Conclusions: A decrease in CD3CD8iNKR cells is observed beyond 6 months of HAART. In some patients functional impairment due to LIR1/ILT2 expression may persist even after 24 months of successful HAART.

Original languageEnglish
Pages (from-to)965-974
Number of pages10
JournalAIDS (London, England)
Volume15
Issue number8
DOIs
Publication statusPublished - May 25 2001

Fingerprint

Natural Killer Cell Receptors
Highly Active Antiretroviral Therapy
Cytotoxic T-Lymphocytes
KIR Receptors
HIV-1
T-Lymphocytes
Lymphocyte Count
Healthy Volunteers
Color
Lymphocytes

Keywords

  • CD8 T lymphocytes
  • Cytotoxic T lymphocytes
  • HAART
  • HIV-1
  • HLA
  • Inhibitory NK receptors
  • KIR

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Differential disappearance of inhibitory natural killer cell receptors during HAART and possible impairment of HIV-1-specific CD8 cytotoxic T lymphocytes. / Costa, Paola; Rusconi, Stefano; Mavilio, Domenico; Fogli, Manuela; Murdaca, Giuseppe; Pende, Daniela; Mingari, Maria Cristina; Galli, Massimo; Moretta, Lorenzo; De Maria, Andrea.

In: AIDS (London, England), Vol. 15, No. 8, 25.05.2001, p. 965-974.

Research output: Contribution to journalArticle

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abstract = "Background: Highly active antiretroviral therapy (HAART) is associated with a decrease in viral replication to undetectable levels and with an increase in CD4 T lymphocytes. Residual HIV-1 replication occurs together with incomplete recovery of cytotoxic CD8 T lymphocyte (CTL) numbers and function. We sought to determine whether expression of HLA class I-specific inhibitory natural killer receptors (iNKR) on the CTL of patients who had been treated successfully with HAART for 24 months could be involved, at least in part, in residual CTL functional inhibition. Methods: Two-colour cytofluorometry was used to analyse the expression of six different iNKR including p58.1, p58.2, p70, p140, CD94/NKG2A and LIR1/ILT2 on the CD3, CD8 lymphocytes of eight patients with successful long-term suppression of viral replication before and after 3, 6 and 24 months of HAART. Healthy subjects were analysed as controls. HIV-1 -specific cytotoxic activity was determined after 24 months of HAART in the presence and absence of iNKR-masking. Results: No significant reduction of iNKR expression on CD8 T cells was observed by 6 months. Expression of p70 and p140 was inversely correlated with the increasing CD4 numbers. After 24 months CD8 T-lymphocytes expressing p58.1, p58.2, p70, p140 and CD94/NKG2A returned to levels indistinguishable from those of the healthy controls. A significantly increased proportion of CD8 CTL still expressed LIR1/ILT2, a receptor with broad HLA-class I specificity. Functional analysis of freshly separated cells revealed that the disruption of the interaction between LIR1/ILT2 and HLA-class I could partly restore HIV-1-specific lysis. Conclusions: A decrease in CD3CD8iNKR cells is observed beyond 6 months of HAART. In some patients functional impairment due to LIR1/ILT2 expression may persist even after 24 months of successful HAART.",
keywords = "CD8 T lymphocytes, Cytotoxic T lymphocytes, HAART, HIV-1, HLA, Inhibitory NK receptors, KIR",
author = "Paola Costa and Stefano Rusconi and Domenico Mavilio and Manuela Fogli and Giuseppe Murdaca and Daniela Pende and Mingari, {Maria Cristina} and Massimo Galli and Lorenzo Moretta and {De Maria}, Andrea",
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T1 - Differential disappearance of inhibitory natural killer cell receptors during HAART and possible impairment of HIV-1-specific CD8 cytotoxic T lymphocytes

AU - Costa, Paola

AU - Rusconi, Stefano

AU - Mavilio, Domenico

AU - Fogli, Manuela

AU - Murdaca, Giuseppe

AU - Pende, Daniela

AU - Mingari, Maria Cristina

AU - Galli, Massimo

AU - Moretta, Lorenzo

AU - De Maria, Andrea

PY - 2001/5/25

Y1 - 2001/5/25

N2 - Background: Highly active antiretroviral therapy (HAART) is associated with a decrease in viral replication to undetectable levels and with an increase in CD4 T lymphocytes. Residual HIV-1 replication occurs together with incomplete recovery of cytotoxic CD8 T lymphocyte (CTL) numbers and function. We sought to determine whether expression of HLA class I-specific inhibitory natural killer receptors (iNKR) on the CTL of patients who had been treated successfully with HAART for 24 months could be involved, at least in part, in residual CTL functional inhibition. Methods: Two-colour cytofluorometry was used to analyse the expression of six different iNKR including p58.1, p58.2, p70, p140, CD94/NKG2A and LIR1/ILT2 on the CD3, CD8 lymphocytes of eight patients with successful long-term suppression of viral replication before and after 3, 6 and 24 months of HAART. Healthy subjects were analysed as controls. HIV-1 -specific cytotoxic activity was determined after 24 months of HAART in the presence and absence of iNKR-masking. Results: No significant reduction of iNKR expression on CD8 T cells was observed by 6 months. Expression of p70 and p140 was inversely correlated with the increasing CD4 numbers. After 24 months CD8 T-lymphocytes expressing p58.1, p58.2, p70, p140 and CD94/NKG2A returned to levels indistinguishable from those of the healthy controls. A significantly increased proportion of CD8 CTL still expressed LIR1/ILT2, a receptor with broad HLA-class I specificity. Functional analysis of freshly separated cells revealed that the disruption of the interaction between LIR1/ILT2 and HLA-class I could partly restore HIV-1-specific lysis. Conclusions: A decrease in CD3CD8iNKR cells is observed beyond 6 months of HAART. In some patients functional impairment due to LIR1/ILT2 expression may persist even after 24 months of successful HAART.

AB - Background: Highly active antiretroviral therapy (HAART) is associated with a decrease in viral replication to undetectable levels and with an increase in CD4 T lymphocytes. Residual HIV-1 replication occurs together with incomplete recovery of cytotoxic CD8 T lymphocyte (CTL) numbers and function. We sought to determine whether expression of HLA class I-specific inhibitory natural killer receptors (iNKR) on the CTL of patients who had been treated successfully with HAART for 24 months could be involved, at least in part, in residual CTL functional inhibition. Methods: Two-colour cytofluorometry was used to analyse the expression of six different iNKR including p58.1, p58.2, p70, p140, CD94/NKG2A and LIR1/ILT2 on the CD3, CD8 lymphocytes of eight patients with successful long-term suppression of viral replication before and after 3, 6 and 24 months of HAART. Healthy subjects were analysed as controls. HIV-1 -specific cytotoxic activity was determined after 24 months of HAART in the presence and absence of iNKR-masking. Results: No significant reduction of iNKR expression on CD8 T cells was observed by 6 months. Expression of p70 and p140 was inversely correlated with the increasing CD4 numbers. After 24 months CD8 T-lymphocytes expressing p58.1, p58.2, p70, p140 and CD94/NKG2A returned to levels indistinguishable from those of the healthy controls. A significantly increased proportion of CD8 CTL still expressed LIR1/ILT2, a receptor with broad HLA-class I specificity. Functional analysis of freshly separated cells revealed that the disruption of the interaction between LIR1/ILT2 and HLA-class I could partly restore HIV-1-specific lysis. Conclusions: A decrease in CD3CD8iNKR cells is observed beyond 6 months of HAART. In some patients functional impairment due to LIR1/ILT2 expression may persist even after 24 months of successful HAART.

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KW - Cytotoxic T lymphocytes

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KW - HIV-1

KW - HLA

KW - Inhibitory NK receptors

KW - KIR

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