TCR/CD3 ligation of a TCR-transgenic T lymphoma blocks its proliferation in vitro but does not affect its growth in vivo.
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.
Institute of Medical Microbiology and Immunology, University of Ulm, Germany.
J
J
Reimann
A
A
Rudolphi
G
G
Tcherepnev
S
S
Skov
M H
MH
Claesson
D000818:Animals; D002455:Cell Division / Q000276:immunology; D002999:Clone Cells / Q000166:cytology / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D006183:H-2 Antigens / Q000276:immunology; D016399:Lymphoma, T-Cell / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D016513:Mice, SCID / Q000276:immunology*; D008822:Mice, Transgenic; D009368:Neoplasm Transplantation / Q000276:immunology / Q000473:pathology; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000378:metabolism / Q000502:physiology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics* / Q000276:immunology; D013953:Thymus Neoplasms / Q000276:immunology / Q000473:pathology; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000276:immunology*
D006183:H-2 Antigens; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta