Oligoclonal expansion of V beta 8+ cells in interleukin-2-activated T cells residing in subcutaneous metastatic melanoma.
Oligoclonality was investigated in interleukin-2 (IL-2)-activated T cells (tumor-infiltrating lymphocytes, TILs) residing in metastatic melanomas using seven different monoclonal antibodies (mAbs) specific for T-cell receptor (TCR) V alpha or V beta regions and flow cytometry. IL-2-activated TILs from 25 of 42 metastatic melanomas (60%) displayed oligoclonal expansion, whereas IL-2-activated peripheral bllod mononuclear cells (PBMCs) from only 2 of 20 patients (10%) did so during 2-5 weeks in culture. Skin-derived lymphocytes from 20 patients were cultured; only four samples proliferated and none showed oligoclonal expansion. Preferential oligoclonal expansion of TILs was observed in V beta 8+ cells (10/42, P less than 0.05), V beta 6.7+ cells (7/42, P less than 0.05), and V alpha 2+ cells (7/42, not significant). Oligoclonal expansion of V beta 8+ cells was primarily found in T cells from subcutaneous metastases (8/20 cases, P less than 0.05), whereas that of V beta 6.7+ cells and V alpha 2+ cells was also found in T cells from lymph node or organ metastases. These mAbs to TCR V regions stimulated effector TILs to produce interferon-gamma, but not IL-2 or IL-4. Subcutaneous tumor-specific (V beta 8+ cells) and non-specific (V beta 6.7+ cells and V alpha 2+ cells) oligoclonalities were observed in IL-2-activated melanoma TILs, suggesting different immune responses among different sites of metastases.
Morita
T
T
Department of Immunology, University of Texas M.D. Anderson Cancer Center, Houston 77030.
Salmeron
M A
MA
Moser
R P
RP
Ross
M I
MI
Itoh
K
K
D000911:Antibodies, Monoclonal / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000276:immunology*; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008545:Melanoma / Q000276:immunology*; D009362:Neoplasm Metastasis / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis* / Q000378:metabolism
D000911:Antibodies, Monoclonal; D007376:Interleukin-2; D016693:Receptors, Antigen, T-Cell, alpha-beta; D007371:Interferon-gamma