Mycobacterium tuberculosis-reactive CD8+ T lymphocytes

The relative contribution of classical versus nonclassical HLA restriction

David Lewinsohn, Andria L. Briden, Steven G. Reed, Kenneth H. Grabstein, Mark R. Alderson

Research output: Contribution to journalArticle

81 Citations (Scopus)

Abstract

Previous studies in mice and humans models have suggested an important role for CD8+ T cells in host defense to Mycobacterium tuberculosis (Mtb). In humans, CD8+ Mtb-reactive T cells have been described that are HLA-A2-, B52-, as well as CD1-restricted. Recently, we have described Mtb-specific CD8+ T cells that are neither HLA-A-, B-, or C- nor group 1 CD1-restricted. At present, little is known about the relative contribution of each of these restriction specificities to the overall CD8+ response to Mtb. An IFN-γ enzyme-linked immunospot assay was used to determine the frequency of Mtb- reactive CD8+ T cells directly from PBMC. The effector cell frequency among five healthy purified protein derivative-positive subjects was 1/7,600 ± 4,300 compared with 1/16,000 ± 7,000 in six purified protein derivative- negative controls. To determine the frequencies of classically, CD1-, and nonclassically restricted cells, a limiting dilution analysis was performed. In one purified protein derivative-positive subject, 192 clones were generated using Mtb-infected dendritic cells (DC). Clones were assessed for reactivity against control autologous DC, Mtb-infected autologous DC, and HLA-mismatched CD1+ targets (DC), as well as HLA-mismatched CD1+ targets (macrophages). Of the 96 Mtb-reactive CD8+ T cell clones, four (4%) were classically restricted and 92 (96%) were nonclassically restricted. CD1- restricted cells were not detected. Of the classically restricted cells, two were HLA-B44 restricted and one was HLA-B14 restricted. These results suggest that while classically restricted CD8+ lymphocytes can be detected, they comprise a relatively small component of the overall CD8+ T cell response to Mtb. Further definition of the nonclassical response may aid development of an effective vaccine against tuberculosis.

Original languageEnglish (US)
Pages (from-to)925-930
Number of pages6
JournalJournal of Immunology
Volume165
Issue number2
StatePublished - Jul 15 2000
Externally publishedYes

Fingerprint

Mycobacterium tuberculosis
T-Lymphocytes
Dendritic Cells
Clone Cells
HLA-B52 Antigen
HLA-B14 Antigen
HLA-B44 Antigen
Tuberculosis Vaccines
HLA-C Antigens
HLA-A2 Antigen
Enzyme-Linked Immunospot Assay
Proteins
HLA-A Antigens
HLA-B Antigens
Macrophages
Lymphocytes

ASJC Scopus subject areas

  • Immunology

Cite this

Mycobacterium tuberculosis-reactive CD8+ T lymphocytes : The relative contribution of classical versus nonclassical HLA restriction. / Lewinsohn, David; Briden, Andria L.; Reed, Steven G.; Grabstein, Kenneth H.; Alderson, Mark R.

In: Journal of Immunology, Vol. 165, No. 2, 15.07.2000, p. 925-930.

Research output: Contribution to journalArticle

Lewinsohn, David ; Briden, Andria L. ; Reed, Steven G. ; Grabstein, Kenneth H. ; Alderson, Mark R. / Mycobacterium tuberculosis-reactive CD8+ T lymphocytes : The relative contribution of classical versus nonclassical HLA restriction. In: Journal of Immunology. 2000 ; Vol. 165, No. 2. pp. 925-930.
@article{b38889e8c67c42eb9df438155fa0224b,
title = "Mycobacterium tuberculosis-reactive CD8+ T lymphocytes: The relative contribution of classical versus nonclassical HLA restriction",
abstract = "Previous studies in mice and humans models have suggested an important role for CD8+ T cells in host defense to Mycobacterium tuberculosis (Mtb). In humans, CD8+ Mtb-reactive T cells have been described that are HLA-A2-, B52-, as well as CD1-restricted. Recently, we have described Mtb-specific CD8+ T cells that are neither HLA-A-, B-, or C- nor group 1 CD1-restricted. At present, little is known about the relative contribution of each of these restriction specificities to the overall CD8+ response to Mtb. An IFN-γ enzyme-linked immunospot assay was used to determine the frequency of Mtb- reactive CD8+ T cells directly from PBMC. The effector cell frequency among five healthy purified protein derivative-positive subjects was 1/7,600 ± 4,300 compared with 1/16,000 ± 7,000 in six purified protein derivative- negative controls. To determine the frequencies of classically, CD1-, and nonclassically restricted cells, a limiting dilution analysis was performed. In one purified protein derivative-positive subject, 192 clones were generated using Mtb-infected dendritic cells (DC). Clones were assessed for reactivity against control autologous DC, Mtb-infected autologous DC, and HLA-mismatched CD1+ targets (DC), as well as HLA-mismatched CD1+ targets (macrophages). Of the 96 Mtb-reactive CD8+ T cell clones, four (4{\%}) were classically restricted and 92 (96{\%}) were nonclassically restricted. CD1- restricted cells were not detected. Of the classically restricted cells, two were HLA-B44 restricted and one was HLA-B14 restricted. These results suggest that while classically restricted CD8+ lymphocytes can be detected, they comprise a relatively small component of the overall CD8+ T cell response to Mtb. Further definition of the nonclassical response may aid development of an effective vaccine against tuberculosis.",
author = "David Lewinsohn and Briden, {Andria L.} and Reed, {Steven G.} and Grabstein, {Kenneth H.} and Alderson, {Mark R.}",
year = "2000",
month = "7",
day = "15",
language = "English (US)",
volume = "165",
pages = "925--930",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "2",

}

TY - JOUR

T1 - Mycobacterium tuberculosis-reactive CD8+ T lymphocytes

T2 - The relative contribution of classical versus nonclassical HLA restriction

AU - Lewinsohn, David

AU - Briden, Andria L.

AU - Reed, Steven G.

AU - Grabstein, Kenneth H.

AU - Alderson, Mark R.

PY - 2000/7/15

Y1 - 2000/7/15

N2 - Previous studies in mice and humans models have suggested an important role for CD8+ T cells in host defense to Mycobacterium tuberculosis (Mtb). In humans, CD8+ Mtb-reactive T cells have been described that are HLA-A2-, B52-, as well as CD1-restricted. Recently, we have described Mtb-specific CD8+ T cells that are neither HLA-A-, B-, or C- nor group 1 CD1-restricted. At present, little is known about the relative contribution of each of these restriction specificities to the overall CD8+ response to Mtb. An IFN-γ enzyme-linked immunospot assay was used to determine the frequency of Mtb- reactive CD8+ T cells directly from PBMC. The effector cell frequency among five healthy purified protein derivative-positive subjects was 1/7,600 ± 4,300 compared with 1/16,000 ± 7,000 in six purified protein derivative- negative controls. To determine the frequencies of classically, CD1-, and nonclassically restricted cells, a limiting dilution analysis was performed. In one purified protein derivative-positive subject, 192 clones were generated using Mtb-infected dendritic cells (DC). Clones were assessed for reactivity against control autologous DC, Mtb-infected autologous DC, and HLA-mismatched CD1+ targets (DC), as well as HLA-mismatched CD1+ targets (macrophages). Of the 96 Mtb-reactive CD8+ T cell clones, four (4%) were classically restricted and 92 (96%) were nonclassically restricted. CD1- restricted cells were not detected. Of the classically restricted cells, two were HLA-B44 restricted and one was HLA-B14 restricted. These results suggest that while classically restricted CD8+ lymphocytes can be detected, they comprise a relatively small component of the overall CD8+ T cell response to Mtb. Further definition of the nonclassical response may aid development of an effective vaccine against tuberculosis.

AB - Previous studies in mice and humans models have suggested an important role for CD8+ T cells in host defense to Mycobacterium tuberculosis (Mtb). In humans, CD8+ Mtb-reactive T cells have been described that are HLA-A2-, B52-, as well as CD1-restricted. Recently, we have described Mtb-specific CD8+ T cells that are neither HLA-A-, B-, or C- nor group 1 CD1-restricted. At present, little is known about the relative contribution of each of these restriction specificities to the overall CD8+ response to Mtb. An IFN-γ enzyme-linked immunospot assay was used to determine the frequency of Mtb- reactive CD8+ T cells directly from PBMC. The effector cell frequency among five healthy purified protein derivative-positive subjects was 1/7,600 ± 4,300 compared with 1/16,000 ± 7,000 in six purified protein derivative- negative controls. To determine the frequencies of classically, CD1-, and nonclassically restricted cells, a limiting dilution analysis was performed. In one purified protein derivative-positive subject, 192 clones were generated using Mtb-infected dendritic cells (DC). Clones were assessed for reactivity against control autologous DC, Mtb-infected autologous DC, and HLA-mismatched CD1+ targets (DC), as well as HLA-mismatched CD1+ targets (macrophages). Of the 96 Mtb-reactive CD8+ T cell clones, four (4%) were classically restricted and 92 (96%) were nonclassically restricted. CD1- restricted cells were not detected. Of the classically restricted cells, two were HLA-B44 restricted and one was HLA-B14 restricted. These results suggest that while classically restricted CD8+ lymphocytes can be detected, they comprise a relatively small component of the overall CD8+ T cell response to Mtb. Further definition of the nonclassical response may aid development of an effective vaccine against tuberculosis.

UR - http://www.scopus.com/inward/record.url?scp=0034661720&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034661720&partnerID=8YFLogxK

M3 - Article

VL - 165

SP - 925

EP - 930

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 2

ER -