Innate T cell immunity to HIV-infection: Immunotherapy with phosphocarbohydrates, a novel strategy of immune intervention?

M. L. Gougeon, M. Malkovsky, R. Casetti, C. Agrati, F. Poccia

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Natural T (NT) lymphocytes recognize infected cells or microbial compounds without the classical genetic restriction of polymorphic major histocompatibility complex (MHC) molecules. NT cells are mainly composed of αβ and γδ T lymphocytes that express natural killer (NK) receptors and recognize preferentially various nonpeptidic antigens. Similar to NK cells, NT lymphocytes can see and kill target cells deficient in the expression of one or more MHC class I molecules. NT cells expressing the αβ TCR can recognize lipid and lipoglycan antigens presented in the context of nonpolymorphic CD1 molecules, whereas phosphocarbohydrates and alkylamines induce constitutive response of Vγ9Vδ2 T cells. The stimulation of Vγ9Vδ2 T cells with phosphocarbohydrates induces the production of cytokines (IFNγ and TNFα) and the release of chemokines with suppressive activity on HIV replication. In addition, stimulated Vγ9Vδ2 T cells exert a cytolytic activity against HIV-infected targets. In HIV-infected patients, a quantitative and qualitative alteration is observed early during the infection. Vγ9Vδ2 T cells are deleted and the remaining γδ cells are anergic. Th1 cytokines (IL-12 and IL-15) positively regulate cytokine production by Vγ9Vδ2 T cells but they are inefficient in restoring normal functions in patients' γδ T cells. Interestingly, partial restoration of the immune system under highly active antiretroviral therapies (HAART) is associated to the recovery of functional Vγ9Vδ2 T cells. A large panel of phosphocarbohydrates able to selectively stimulate Vγ9Vδ2 T cells is currently available, and preliminary experiments in monkeys suggest their in vivo efficacy in helping to control SIV replication. These observations prompt the question of new immune intervention involving molecules that stimulate NT cells.

Original languageEnglish
Pages (from-to)1938-1941
Number of pages4
JournalVaccine
Volume20
Issue number15
DOIs
Publication statusPublished - May 6 2002

Fingerprint

immunotherapy
HIV infections
Immunotherapy
HIV Infections
Immunity
T-lymphocytes
immunity
T-Lymphocytes
cytokines
HIV
major histocompatibility complex
Cytokines
Major Histocompatibility Complex
antigens
Antigens
Interleukin-15
interleukin-12
Highly Active Antiretroviral Therapy
natural killer cells
cells

Keywords

  • γδ T cells-HIV
  • Phosphocarbohydrates

ASJC Scopus subject areas

  • Immunology
  • Microbiology
  • Virology
  • Infectious Diseases
  • Public Health, Environmental and Occupational Health
  • veterinary(all)

Cite this

Innate T cell immunity to HIV-infection : Immunotherapy with phosphocarbohydrates, a novel strategy of immune intervention? / Gougeon, M. L.; Malkovsky, M.; Casetti, R.; Agrati, C.; Poccia, F.

In: Vaccine, Vol. 20, No. 15, 06.05.2002, p. 1938-1941.

Research output: Contribution to journalArticle

@article{d231fdf1458f4ca3a66386fcd069c8e1,
title = "Innate T cell immunity to HIV-infection: Immunotherapy with phosphocarbohydrates, a novel strategy of immune intervention?",
abstract = "Natural T (NT) lymphocytes recognize infected cells or microbial compounds without the classical genetic restriction of polymorphic major histocompatibility complex (MHC) molecules. NT cells are mainly composed of αβ and γδ T lymphocytes that express natural killer (NK) receptors and recognize preferentially various nonpeptidic antigens. Similar to NK cells, NT lymphocytes can see and kill target cells deficient in the expression of one or more MHC class I molecules. NT cells expressing the αβ TCR can recognize lipid and lipoglycan antigens presented in the context of nonpolymorphic CD1 molecules, whereas phosphocarbohydrates and alkylamines induce constitutive response of Vγ9Vδ2 T cells. The stimulation of Vγ9Vδ2 T cells with phosphocarbohydrates induces the production of cytokines (IFNγ and TNFα) and the release of chemokines with suppressive activity on HIV replication. In addition, stimulated Vγ9Vδ2 T cells exert a cytolytic activity against HIV-infected targets. In HIV-infected patients, a quantitative and qualitative alteration is observed early during the infection. Vγ9Vδ2 T cells are deleted and the remaining γδ cells are anergic. Th1 cytokines (IL-12 and IL-15) positively regulate cytokine production by Vγ9Vδ2 T cells but they are inefficient in restoring normal functions in patients' γδ T cells. Interestingly, partial restoration of the immune system under highly active antiretroviral therapies (HAART) is associated to the recovery of functional Vγ9Vδ2 T cells. A large panel of phosphocarbohydrates able to selectively stimulate Vγ9Vδ2 T cells is currently available, and preliminary experiments in monkeys suggest their in vivo efficacy in helping to control SIV replication. These observations prompt the question of new immune intervention involving molecules that stimulate NT cells.",
keywords = "γδ T cells-HIV, Phosphocarbohydrates",
author = "Gougeon, {M. L.} and M. Malkovsky and R. Casetti and C. Agrati and F. Poccia",
year = "2002",
month = "5",
day = "6",
doi = "10.1016/S0264-410X(02)00070-1",
language = "English",
volume = "20",
pages = "1938--1941",
journal = "Vaccine",
issn = "0264-410X",
publisher = "Elsevier BV",
number = "15",

}

TY - JOUR

T1 - Innate T cell immunity to HIV-infection

T2 - Immunotherapy with phosphocarbohydrates, a novel strategy of immune intervention?

AU - Gougeon, M. L.

AU - Malkovsky, M.

AU - Casetti, R.

AU - Agrati, C.

AU - Poccia, F.

PY - 2002/5/6

Y1 - 2002/5/6

N2 - Natural T (NT) lymphocytes recognize infected cells or microbial compounds without the classical genetic restriction of polymorphic major histocompatibility complex (MHC) molecules. NT cells are mainly composed of αβ and γδ T lymphocytes that express natural killer (NK) receptors and recognize preferentially various nonpeptidic antigens. Similar to NK cells, NT lymphocytes can see and kill target cells deficient in the expression of one or more MHC class I molecules. NT cells expressing the αβ TCR can recognize lipid and lipoglycan antigens presented in the context of nonpolymorphic CD1 molecules, whereas phosphocarbohydrates and alkylamines induce constitutive response of Vγ9Vδ2 T cells. The stimulation of Vγ9Vδ2 T cells with phosphocarbohydrates induces the production of cytokines (IFNγ and TNFα) and the release of chemokines with suppressive activity on HIV replication. In addition, stimulated Vγ9Vδ2 T cells exert a cytolytic activity against HIV-infected targets. In HIV-infected patients, a quantitative and qualitative alteration is observed early during the infection. Vγ9Vδ2 T cells are deleted and the remaining γδ cells are anergic. Th1 cytokines (IL-12 and IL-15) positively regulate cytokine production by Vγ9Vδ2 T cells but they are inefficient in restoring normal functions in patients' γδ T cells. Interestingly, partial restoration of the immune system under highly active antiretroviral therapies (HAART) is associated to the recovery of functional Vγ9Vδ2 T cells. A large panel of phosphocarbohydrates able to selectively stimulate Vγ9Vδ2 T cells is currently available, and preliminary experiments in monkeys suggest their in vivo efficacy in helping to control SIV replication. These observations prompt the question of new immune intervention involving molecules that stimulate NT cells.

AB - Natural T (NT) lymphocytes recognize infected cells or microbial compounds without the classical genetic restriction of polymorphic major histocompatibility complex (MHC) molecules. NT cells are mainly composed of αβ and γδ T lymphocytes that express natural killer (NK) receptors and recognize preferentially various nonpeptidic antigens. Similar to NK cells, NT lymphocytes can see and kill target cells deficient in the expression of one or more MHC class I molecules. NT cells expressing the αβ TCR can recognize lipid and lipoglycan antigens presented in the context of nonpolymorphic CD1 molecules, whereas phosphocarbohydrates and alkylamines induce constitutive response of Vγ9Vδ2 T cells. The stimulation of Vγ9Vδ2 T cells with phosphocarbohydrates induces the production of cytokines (IFNγ and TNFα) and the release of chemokines with suppressive activity on HIV replication. In addition, stimulated Vγ9Vδ2 T cells exert a cytolytic activity against HIV-infected targets. In HIV-infected patients, a quantitative and qualitative alteration is observed early during the infection. Vγ9Vδ2 T cells are deleted and the remaining γδ cells are anergic. Th1 cytokines (IL-12 and IL-15) positively regulate cytokine production by Vγ9Vδ2 T cells but they are inefficient in restoring normal functions in patients' γδ T cells. Interestingly, partial restoration of the immune system under highly active antiretroviral therapies (HAART) is associated to the recovery of functional Vγ9Vδ2 T cells. A large panel of phosphocarbohydrates able to selectively stimulate Vγ9Vδ2 T cells is currently available, and preliminary experiments in monkeys suggest their in vivo efficacy in helping to control SIV replication. These observations prompt the question of new immune intervention involving molecules that stimulate NT cells.

KW - γδ T cells-HIV

KW - Phosphocarbohydrates

UR - http://www.scopus.com/inward/record.url?scp=0037029903&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037029903&partnerID=8YFLogxK

U2 - 10.1016/S0264-410X(02)00070-1

DO - 10.1016/S0264-410X(02)00070-1

M3 - Article

C2 - 11983250

AN - SCOPUS:0037029903

VL - 20

SP - 1938

EP - 1941

JO - Vaccine

JF - Vaccine

SN - 0264-410X

IS - 15

ER -