TCR/CD3 ligation of a TCR-transgenic T lymphoma blocks its proliferation in vitro but does not affect its growth in vivo
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TCR/CD3 ligation of a TCR-transgenic T lymphoma blocks its proliferation in vitro but does not affect its growth in vivo. / Reimann, J; Rudolphi, A; Tcherepnev, G; Skov, S; Claesson, Mogens Helweg.
I: Experimental and Clinical Immunogenetics, Bind 11, Nr. 4, 1994, s. 197-208.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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T1 - TCR/CD3 ligation of a TCR-transgenic T lymphoma blocks its proliferation in vitro but does not affect its growth in vivo
AU - Reimann, J
AU - Rudolphi, A
AU - Tcherepnev, G
AU - Skov, S
AU - Claesson, Mogens Helweg
PY - 1994
Y1 - 1994
N2 - A backcrossed mouse line was established homozygous for the autosomal recessive mutation scid (severe combined immunodeficiency) and carrying T cells which express transgenic (tg) T cell receptor (TCR) alpha and beta chains that mediate H-2 class I (Db)-restricted recognition of a male (H-Y) determinant (TCR-tg SCID mouse). A thymoma arose 'spontaneously' in one of the TCR-tg female SCID mice and the thymoma cells were adopted to factor-independent, in vitro growth in long-term tissue culture. The thymic lymphoma cell line was cloned and one of the subclones, TL1, was studied. The ultrastructure of TL1 cells resembled that of small-to-medium lymphoblasts. The cells had the following phenotype: CD3 + TCR alpha T+TCR beta T+CD4-CD8- CD44-CD45RB+LECAM-1 + IL-2R- and low H-2 expression. Exposure of TL1 cells to TCR-binding monoclonal antibodies or lectins blocked in their in vitro proliferation. In addition, TL1 cell proliferation was inhibited by coculture with male and female H-2b+ cells. Following adoptive transfer into both H-2b+ and H-2d+ SCID recipient mice, TL1 cells showed rapid, malignant growth and infiltrated lymphoid and nonlymphoid organs. Expression of the tg TCR complex was selectively downregulated in TL1 cells growing in H-2b+ male SCID recipients. However, the malignant in vivo growth potential of TL1 cells was comparable, irrespectively of the sex and haplotype of the SCID recipient. In conclusion, our data show that the growth of TL1 cells in vitro is suppressed by physiological ligation of their TCR complex, whereas TL1 cells, by downregulation of their TCR, may escape TCR-ligation-induced suppression in vivo.
AB - A backcrossed mouse line was established homozygous for the autosomal recessive mutation scid (severe combined immunodeficiency) and carrying T cells which express transgenic (tg) T cell receptor (TCR) alpha and beta chains that mediate H-2 class I (Db)-restricted recognition of a male (H-Y) determinant (TCR-tg SCID mouse). A thymoma arose 'spontaneously' in one of the TCR-tg female SCID mice and the thymoma cells were adopted to factor-independent, in vitro growth in long-term tissue culture. The thymic lymphoma cell line was cloned and one of the subclones, TL1, was studied. The ultrastructure of TL1 cells resembled that of small-to-medium lymphoblasts. The cells had the following phenotype: CD3 + TCR alpha T+TCR beta T+CD4-CD8- CD44-CD45RB+LECAM-1 + IL-2R- and low H-2 expression. Exposure of TL1 cells to TCR-binding monoclonal antibodies or lectins blocked in their in vitro proliferation. In addition, TL1 cell proliferation was inhibited by coculture with male and female H-2b+ cells. Following adoptive transfer into both H-2b+ and H-2d+ SCID recipient mice, TL1 cells showed rapid, malignant growth and infiltrated lymphoid and nonlymphoid organs. Expression of the tg TCR complex was selectively downregulated in TL1 cells growing in H-2b+ male SCID recipients. However, the malignant in vivo growth potential of TL1 cells was comparable, irrespectively of the sex and haplotype of the SCID recipient. In conclusion, our data show that the growth of TL1 cells in vitro is suppressed by physiological ligation of their TCR complex, whereas TL1 cells, by downregulation of their TCR, may escape TCR-ligation-induced suppression in vivo.
KW - Animals
KW - Cell Division
KW - Clone Cells
KW - Female
KW - Flow Cytometry
KW - H-2 Antigens
KW - Lymphoma, T-Cell
KW - Male
KW - Mice
KW - Mice, SCID
KW - Mice, Transgenic
KW - Neoplasm Transplantation
KW - Receptor-CD3 Complex, Antigen, T-Cell
KW - Receptors, Antigen, T-Cell, alpha-beta
KW - Thymus Neoplasms
KW - Tumor Cells, Cultured
M3 - Journal article
C2 - 7857666
VL - 11
SP - 197
EP - 208
JO - Experimental and Clinical Immunogenetics
JF - Experimental and Clinical Immunogenetics
SN - 0254-9670
IS - 4
ER -
ID: 252630