TCR/CD3 ligation of a TCR-transgenic T lymphoma blocks its proliferation in vitro but does not affect its growth in vivo

TY - JOUR

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

SN - 0254-9670

VL - 11

SP - 197

EP - 208

JO - Experimental and Clinical Immunogenetics

JF - Experimental and Clinical Immunogenetics

IS - 4

ER -