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Classification of CD4+ T helper cell clones in human melanoma. 1994

P S Goedegebuure, and K Y Lee, and Y L Matory, and G E Peoples, and I Yoshino, and T J Eberlein
Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115.

We have previously described the generation of tumor-infiltrating lymphocyte (TIL) clones from renal cell cancer by solid-phase anti-CD3 antibody activation and expansion in 100 IU/ml IL-2 plus irradiated allogeneic B cells. These culture conditions did not select for a particular T cell subset. Using these culture conditions, we report here the generation of 66 CD4+ and 36 CD8+ TIL clones from five patients with melanoma. Eighty-five percent of the CD4+ TIL clones were not cytolytic (< 30% lysis, E:T 20:1) as determined by antibody-redirected lysis (ARL), whereas all CD8+ clones showed strong ARL activity (> 30% lysis). Clones were further tested for production of IL-2, IL-4, and IFN-gamma after activation for 48 hr by solid-phase anti-CD3. CD8+ clones produced significant amounts of IFN-gamma, little IL-2, and no IL-4. CD4+ clones were classified as Th0, Th1, or Th2, analogous to the classification of T helper cells in the mouse. Sixty-six percent existed as Th0, producing IL-2, IL-4, and IFN-gamma. Only 15% existed as Th1, producing IL-2 and IFN-gamma, and 19% as Th2, producing IL-4 but no IL-2 or IFN-gamma. In all cases, unstimulated clones or clones stimulated with the allogeneic B cell line did not produce detectable amounts of cytokines. Solid-phase anti-CD3 activation was compared to activation with autologous melanoma cells. Five of nine CD8+ clones produced low amounts of IL-2 (< 200 pg/ml/10(6) cells) in response to autologous tumor, but none of the CD8 clones produced IFN-gamma or IL-4. Also, 5/7 Th0 clones from one patient produced similar amounts of IL-2 after stimulation with anti-CD3 or autologous tumor. The other two clones produced only 10% or less of the amount produced in response to anti-CD3. No IL-4 or IFN-gamma could be detected in response to autologous tumor. In contrast, none of the 12 T helper clones from two other patients produced any cytokines after stimulation with autologous tumor cells. Together these data suggest that the T cell infiltrate in melanoma consists primarily of IL-2-producing Th0 cells, but few of those are triggered by autologous tumor cells.

UI MeSH Term Description Entries
D008545 Melanoma A malignant neoplasm derived from cells that are capable of forming melanin, which may occur in the skin of any part of the body, in the eye, or, rarely, in the mucous membranes of the genitalia, anus, oral cavity, or other sites. It occurs mostly in adults and may originate de novo or from a pigmented nevus or malignant lentigo. Melanomas frequently metastasize widely, and the regional lymph nodes, liver, lungs, and brain are likely to be involved. The incidence of malignant skin melanomas is rising rapidly in all parts of the world. (Stedman, 25th ed; from Rook et al., Textbook of Dermatology, 4th ed, p2445) Malignant Melanoma,Malignant Melanomas,Melanoma, Malignant,Melanomas,Melanomas, Malignant
D003602 Cytotoxicity, Immunologic The phenomenon of target cell destruction by immunologically active effector cells. It may be brought about directly by sensitized T-lymphocytes or by lymphoid or myeloid "killer" cells, or it may be mediated by cytotoxic antibody, cytotoxic factor released by lymphoid cells, or complement. Tumoricidal Activity, Immunologic,Immunologic Cytotoxicity,Immunologic Tumoricidal Activities,Immunologic Tumoricidal Activity,Tumoricidal Activities, Immunologic
D006377 T-Lymphocytes, Helper-Inducer Subpopulation of CD4+ lymphocytes that cooperate with other lymphocytes (either T or B) to initiate a variety of immune functions. For example, helper-inducer T-cells cooperate with B-cells to produce antibodies to thymus-dependent antigens and with other subpopulations of T-cells to initiate a variety of cell-mediated immune functions. Helper Cell,Helper Cells,Helper T Cell,Helper-Inducer T-Lymphocytes,Inducer Cell,Inducer Cells,T-Cells, Helper-Inducer,T-Lymphocytes, Helper,T-Lymphocytes, Inducer,Helper T-Cells,Cell, Helper T,Cells, Helper T,Helper Inducer T Lymphocytes,Helper T Cells,Helper T-Cell,Helper T-Lymphocyte,Helper T-Lymphocytes,Helper-Inducer T-Cell,Helper-Inducer T-Cells,Helper-Inducer T-Lymphocyte,Inducer T-Lymphocyte,Inducer T-Lymphocytes,T Cell, Helper,T Cells, Helper,T Cells, Helper Inducer,T Lymphocytes, Helper,T Lymphocytes, Helper Inducer,T Lymphocytes, Inducer,T-Cell, Helper,T-Cell, Helper-Inducer,T-Cells, Helper,T-Lymphocyte, Helper,T-Lymphocyte, Helper-Inducer,T-Lymphocyte, Inducer
D006681 HLA-D Antigens Human immune-response or Class II antigens found mainly, but not exclusively, on B-lymphocytes and produced from genes of the HLA-D locus. They are extremely polymorphic families of glycopeptides, each consisting of two chains, alpha and beta. This group of antigens includes the -DR, -DQ and -DP designations, of which HLA-DR is most studied; some of these glycoproteins are associated with certain diseases, possibly of immune etiology. Antigens, HLA-D,Class II Human Antigens,HLA-Dw Antigens,Human Class II Antigens,Ia-Like Antigens, Human,Immune Response-Associated Antigens, Human,Immune-Associated Antigens, Human,Immune-Response Antigens, Human,HLA-D,HLA-Dw,Immune Response Associated Antigens, Human,Antigens, HLA D,Antigens, HLA-Dw,Antigens, Human Ia-Like,Antigens, Human Immune-Associated,Antigens, Human Immune-Response,HLA D Antigens,HLA Dw Antigens,Human Ia-Like Antigens,Human Immune-Associated Antigens,Human Immune-Response Antigens,Ia Like Antigens, Human,Immune Associated Antigens, Human,Immune Response Antigens, Human
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D015496 CD4-Positive T-Lymphocytes A critical subpopulation of T-lymphocytes involved in the induction of most immunological functions. The HIV virus has selective tropism for the T4 cell which expresses the CD4 phenotypic marker, a receptor for HIV. In fact, the key element in the profound immunosuppression seen in HIV infection is the depletion of this subset of T-lymphocytes. T4 Cells,T4 Lymphocytes,CD4-Positive Lymphocytes,CD4 Positive T Lymphocytes,CD4-Positive Lymphocyte,CD4-Positive T-Lymphocyte,Lymphocyte, CD4-Positive,Lymphocytes, CD4-Positive,T-Lymphocyte, CD4-Positive,T-Lymphocytes, CD4-Positive,T4 Cell,T4 Lymphocyte
D016176 T-Lymphocyte Subsets A classification of T-lymphocytes, especially into helper/inducer, suppressor/effector, and cytotoxic subsets, based on structurally or functionally different populations of cells. T-Cell Subset,T-Cell Subsets,T-Lymphocyte Subset,Subset, T-Cell,Subset, T-Lymphocyte,Subsets, T-Cell,Subsets, T-Lymphocyte,T Cell Subset,T Cell Subsets,T Lymphocyte Subset,T Lymphocyte Subsets
D016207 Cytokines Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner. Cytokine
D016827 CD8 Antigens Differentiation antigens found on thymocytes and on cytotoxic and suppressor T-lymphocytes. T8 antigens are members of the immunoglobulin supergene family and are associative recognition elements in MHC (Major Histocompatibility Complex) Class I-restricted interactions. Antigens, CD8,Leu-2 Antigens,T8 Antigens, T-Cell,CD8 Antigen,Antigen, CD8,Antigens, Leu-2,Antigens, T-Cell T8,Leu 2 Antigens,T-Cell T8 Antigens,T8 Antigens, T Cell

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