Genotypic analysis of T-cell clones derived from cutaneous T-cell lymphoma lesions demonstrates selective growth of tumor-infiltrating lymphocytes.
The nature of T cells contained within cutaneous lesions of cutaneous T-cell lymphoma (CTCL) has not been studied at the clonal level. T cells extracted from skin lesions of two CTCL patients were cloned by limiting dilution and propagated in interleukin-2 (IL-2) containing medium with periodic lectin stimulation. Twelve T-cell clones were derived from each patient. In both cases, genotypic analysis of the T-cell clones revealed that these clones had T-cell receptor (TCR) beta- and gamma-chain gene rearrangements distinct from the predominant, presumably malignant, clone present in the skin, lymph nodes, or blood. This suggests that they were derived from presumably reactive (non-malignant) T cells. Furthermore, these clones had gene rearrangements different from each other, indicating their multiple clonal origins. The failure to propagate in vitro the CTCL T-cell clone suggests that CTCL cells may have growth requirements different from normal T cells. Thus, conventional T-cell culturing methods using IL-2 and lectins as mitogen may selectively propagate the presumably reactive T cells contained within the skin lesions. The ability to selectively grow these reactive lesional T cells (so-called tumor infiltrating lymphocytes) raises the possibility that these cells could be used in adoptive immunotherapy.
Ho
V C
VC
Department of Dermatology, University of Michigan, Ann Arbor.
Baadsgaard
O
O
Elder
J T
JT
Hansen
E R
ER
Hanson
C A
CA
Vejlsgaard
G L
GL
Cooper
K D
KD
D002455:Cell Division; D002999:Clone Cells; D015321:Gene Rearrangement; D005838:Genotype; D006801:Humans; D008223:Lymphoma / Q000235:genetics / Q000473:pathology*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D012867:Skin / Q000473:pathology*; D012878:Skin Neoplasms / Q000235:genetics / Q000473:pathology*; D013601:T-Lymphocytes / Q000473:pathology / Q000502:physiology*
D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta