Generation and characterization of cloned T helper cell lines for anti-DNA responses in NZB.H-2bm12 mice

Mitsuru Naiki, Bor Luen Chiang, Daniel Cawley, Aftab Ansari, Stephen J. Rozzo, Brian L. Kotzin, Albert Zlotnik, M. Eric Gershwin

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

We have previously demonstrated that the introduction of the bm12 mutation into NZB mice results in animals that spontaneously produce high titer IgG autoantibodies to dsDNA. The observation that NZB.H-2bm12 develop lupus although NZB.H-2b control mice do not, provides a unique system to study the role of Th cells in the production of antibodies to dsDNA. We have isolated, in the absence of a known stimulating autoantigen, a series of seven autoreactive T cell clones that provide help in vitro for the production of IgG anti-dsDNA antibodies by syngeneic B cells. The data on these seven cloned T cell lines was compared to two cloned T cell lines specific for keyhole limpet hemocyanin. The seven cloned T cell lines, coined clones 19D, 23G, 410F, 410H, C1, CIS, and C52 all show significant help in vitro for production of IgM and IgG antibodies to ssDNA and dsDNA; antibody levels increased 7- to 30-fold compared to cultures without T cells. Clones C1, C15, and C52 were furthered studied and were shown to provide help for IgM antihistone and antiOVA responses but provided significantly less help for IgG antibodies. In contrast, keyhole limpet hemocyanin-specific cloned T cell lines TK2 and TK5 provided help for IgM antibodies to ssDNA, dsDNA, and histone, but failed to significantly increase IgG antibodies to ssDNA, dsDNA, or histone. The cloned T cell lines were restricted to H-2bm12 and proliferated only in response to APC from NZB.H-2bm12 and B6.C-H-2bm12 but not NZB.H-2b or NZB.H-2d mice; their in vitro helper activity was inhibited by antibodies to class II. All cloned T cell lines expressed Thy-1, CDS, and TCR-α/β. Three of the seven clones used TCR-Vβ4. However, the Vβ expression of the four remaining autoreactive T cell clones could not be determined. All of the autoreactive cloned T cell lines produce significant IL-4 but no detectable IL-2 or IFN-γ. We believe that HPLC-purified peptides eluted from I-Abm12 molecules from APC can potentially provide insight on the putative autoantigen.

Original languageEnglish (US)
Pages (from-to)4109-4115
Number of pages7
JournalJournal of Immunology
Volume149
Issue number12
StatePublished - 1992
Externally publishedYes

Fingerprint

T-Lymphocytes
Cell Line
DNA
Clone Cells
Immunoglobulin G
Antibodies
Immunoglobulin M
Autoantigens
Histones
Inbred NZB Mouse
Immunoglobulin Isotypes
Interleukin-4
Autoantibodies
Antibody Formation
Interleukin-2
Anti-Idiotypic Antibodies
B-Lymphocytes
High Pressure Liquid Chromatography
Peptides
Mutation

ASJC Scopus subject areas

  • Immunology

Cite this

Naiki, M., Chiang, B. L., Cawley, D., Ansari, A., Rozzo, S. J., Kotzin, B. L., ... Gershwin, M. E. (1992). Generation and characterization of cloned T helper cell lines for anti-DNA responses in NZB.H-2bm12 mice. Journal of Immunology, 149(12), 4109-4115.

Generation and characterization of cloned T helper cell lines for anti-DNA responses in NZB.H-2bm12 mice. / Naiki, Mitsuru; Chiang, Bor Luen; Cawley, Daniel; Ansari, Aftab; Rozzo, Stephen J.; Kotzin, Brian L.; Zlotnik, Albert; Gershwin, M. Eric.

In: Journal of Immunology, Vol. 149, No. 12, 1992, p. 4109-4115.

Research output: Contribution to journalArticle

Naiki, M, Chiang, BL, Cawley, D, Ansari, A, Rozzo, SJ, Kotzin, BL, Zlotnik, A & Gershwin, ME 1992, 'Generation and characterization of cloned T helper cell lines for anti-DNA responses in NZB.H-2bm12 mice', Journal of Immunology, vol. 149, no. 12, pp. 4109-4115.
Naiki M, Chiang BL, Cawley D, Ansari A, Rozzo SJ, Kotzin BL et al. Generation and characterization of cloned T helper cell lines for anti-DNA responses in NZB.H-2bm12 mice. Journal of Immunology. 1992;149(12):4109-4115.
Naiki, Mitsuru ; Chiang, Bor Luen ; Cawley, Daniel ; Ansari, Aftab ; Rozzo, Stephen J. ; Kotzin, Brian L. ; Zlotnik, Albert ; Gershwin, M. Eric. / Generation and characterization of cloned T helper cell lines for anti-DNA responses in NZB.H-2bm12 mice. In: Journal of Immunology. 1992 ; Vol. 149, No. 12. pp. 4109-4115.
@article{f9ec54e915ff4959a7651b23741f8681,
title = "Generation and characterization of cloned T helper cell lines for anti-DNA responses in NZB.H-2bm12 mice",
abstract = "We have previously demonstrated that the introduction of the bm12 mutation into NZB mice results in animals that spontaneously produce high titer IgG autoantibodies to dsDNA. The observation that NZB.H-2bm12 develop lupus although NZB.H-2b control mice do not, provides a unique system to study the role of Th cells in the production of antibodies to dsDNA. We have isolated, in the absence of a known stimulating autoantigen, a series of seven autoreactive T cell clones that provide help in vitro for the production of IgG anti-dsDNA antibodies by syngeneic B cells. The data on these seven cloned T cell lines was compared to two cloned T cell lines specific for keyhole limpet hemocyanin. The seven cloned T cell lines, coined clones 19D, 23G, 410F, 410H, C1, CIS, and C52 all show significant help in vitro for production of IgM and IgG antibodies to ssDNA and dsDNA; antibody levels increased 7- to 30-fold compared to cultures without T cells. Clones C1, C15, and C52 were furthered studied and were shown to provide help for IgM antihistone and antiOVA responses but provided significantly less help for IgG antibodies. In contrast, keyhole limpet hemocyanin-specific cloned T cell lines TK2 and TK5 provided help for IgM antibodies to ssDNA, dsDNA, and histone, but failed to significantly increase IgG antibodies to ssDNA, dsDNA, or histone. The cloned T cell lines were restricted to H-2bm12 and proliferated only in response to APC from NZB.H-2bm12 and B6.C-H-2bm12 but not NZB.H-2b or NZB.H-2d mice; their in vitro helper activity was inhibited by antibodies to class II. All cloned T cell lines expressed Thy-1, CDS, and TCR-α/β. Three of the seven clones used TCR-Vβ4. However, the Vβ expression of the four remaining autoreactive T cell clones could not be determined. All of the autoreactive cloned T cell lines produce significant IL-4 but no detectable IL-2 or IFN-γ. We believe that HPLC-purified peptides eluted from I-Abm12 molecules from APC can potentially provide insight on the putative autoantigen.",
author = "Mitsuru Naiki and Chiang, {Bor Luen} and Daniel Cawley and Aftab Ansari and Rozzo, {Stephen J.} and Kotzin, {Brian L.} and Albert Zlotnik and Gershwin, {M. Eric}",
year = "1992",
language = "English (US)",
volume = "149",
pages = "4109--4115",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "12",

}

TY - JOUR

T1 - Generation and characterization of cloned T helper cell lines for anti-DNA responses in NZB.H-2bm12 mice

AU - Naiki, Mitsuru

AU - Chiang, Bor Luen

AU - Cawley, Daniel

AU - Ansari, Aftab

AU - Rozzo, Stephen J.

AU - Kotzin, Brian L.

AU - Zlotnik, Albert

AU - Gershwin, M. Eric

PY - 1992

Y1 - 1992

N2 - We have previously demonstrated that the introduction of the bm12 mutation into NZB mice results in animals that spontaneously produce high titer IgG autoantibodies to dsDNA. The observation that NZB.H-2bm12 develop lupus although NZB.H-2b control mice do not, provides a unique system to study the role of Th cells in the production of antibodies to dsDNA. We have isolated, in the absence of a known stimulating autoantigen, a series of seven autoreactive T cell clones that provide help in vitro for the production of IgG anti-dsDNA antibodies by syngeneic B cells. The data on these seven cloned T cell lines was compared to two cloned T cell lines specific for keyhole limpet hemocyanin. The seven cloned T cell lines, coined clones 19D, 23G, 410F, 410H, C1, CIS, and C52 all show significant help in vitro for production of IgM and IgG antibodies to ssDNA and dsDNA; antibody levels increased 7- to 30-fold compared to cultures without T cells. Clones C1, C15, and C52 were furthered studied and were shown to provide help for IgM antihistone and antiOVA responses but provided significantly less help for IgG antibodies. In contrast, keyhole limpet hemocyanin-specific cloned T cell lines TK2 and TK5 provided help for IgM antibodies to ssDNA, dsDNA, and histone, but failed to significantly increase IgG antibodies to ssDNA, dsDNA, or histone. The cloned T cell lines were restricted to H-2bm12 and proliferated only in response to APC from NZB.H-2bm12 and B6.C-H-2bm12 but not NZB.H-2b or NZB.H-2d mice; their in vitro helper activity was inhibited by antibodies to class II. All cloned T cell lines expressed Thy-1, CDS, and TCR-α/β. Three of the seven clones used TCR-Vβ4. However, the Vβ expression of the four remaining autoreactive T cell clones could not be determined. All of the autoreactive cloned T cell lines produce significant IL-4 but no detectable IL-2 or IFN-γ. We believe that HPLC-purified peptides eluted from I-Abm12 molecules from APC can potentially provide insight on the putative autoantigen.

AB - We have previously demonstrated that the introduction of the bm12 mutation into NZB mice results in animals that spontaneously produce high titer IgG autoantibodies to dsDNA. The observation that NZB.H-2bm12 develop lupus although NZB.H-2b control mice do not, provides a unique system to study the role of Th cells in the production of antibodies to dsDNA. We have isolated, in the absence of a known stimulating autoantigen, a series of seven autoreactive T cell clones that provide help in vitro for the production of IgG anti-dsDNA antibodies by syngeneic B cells. The data on these seven cloned T cell lines was compared to two cloned T cell lines specific for keyhole limpet hemocyanin. The seven cloned T cell lines, coined clones 19D, 23G, 410F, 410H, C1, CIS, and C52 all show significant help in vitro for production of IgM and IgG antibodies to ssDNA and dsDNA; antibody levels increased 7- to 30-fold compared to cultures without T cells. Clones C1, C15, and C52 were furthered studied and were shown to provide help for IgM antihistone and antiOVA responses but provided significantly less help for IgG antibodies. In contrast, keyhole limpet hemocyanin-specific cloned T cell lines TK2 and TK5 provided help for IgM antibodies to ssDNA, dsDNA, and histone, but failed to significantly increase IgG antibodies to ssDNA, dsDNA, or histone. The cloned T cell lines were restricted to H-2bm12 and proliferated only in response to APC from NZB.H-2bm12 and B6.C-H-2bm12 but not NZB.H-2b or NZB.H-2d mice; their in vitro helper activity was inhibited by antibodies to class II. All cloned T cell lines expressed Thy-1, CDS, and TCR-α/β. Three of the seven clones used TCR-Vβ4. However, the Vβ expression of the four remaining autoreactive T cell clones could not be determined. All of the autoreactive cloned T cell lines produce significant IL-4 but no detectable IL-2 or IFN-γ. We believe that HPLC-purified peptides eluted from I-Abm12 molecules from APC can potentially provide insight on the putative autoantigen.

UR - http://www.scopus.com/inward/record.url?scp=0027101806&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0027101806&partnerID=8YFLogxK

M3 - Article

C2 - 1460294

AN - SCOPUS:0027101806

VL - 149

SP - 4109

EP - 4115

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 12

ER -