T-cell clones that react against autologous human tumors

Abstract

T cells (derived from peripheral blood lymphocytes [PBL], lymph nodes or tumor tissues and restimulated with autologous tumor cells and expanded in interleukin-2 [IL-2]), when cloned, produce three functional classes of clone. Class I T-cell clones exhibit the phenotype of alpha/beta cytotoxic T lymphocytes (CD3+, CD8+, CD4-, WT31+), use their CD3-alpha/beta complexes for cognate function, and lyse the autologous tumor cells specifically in a major histocompatibility complex (MHC) Class I-restricted manner. The second class of T cell clone expresses identical phenotype but exhibits a rather broad cytotoxic profile against the autologous and allogeneic tumor cells derived from tumors with similar and/or dissimilar histologies. Although these CTL clones can, at times, show MHC Class I-restricted killing and use their T-cell receptors (TCR) complexes for function, activation via certain accessory molecules, particularly lymphocyte-function associated (LFA-1) antigens, might induce their broad cytotoxic behavior. The nature of the tumor antigen recognized by the Class I antigen-specific CTL clones remains unknown. It is evident, however, that more than one antigen can be associated with a given tumor and they are recognized by different CTL clones from individual patients. The third class of T-cell clone is usually of CD4+ alpha/beta T cells (CD3+, CD4+, CD8-, WT31) and these T-cell clones exhibit no cytotoxicity toward the autologous or allogeneic target cells. When tested for potential regulatory property, one type of CD4+ T-cell clone exhibits the characteristics of helper T cells. This type induces or amplifies cytotoxic response in fresh PBL by elaborating interleukin-2 (IL-2) and interferon-gamma). These helper T-cell clones can proliferate against the autologous tumor cells and demonstrate functional specificity for the autologous tumor cells. The other type of CD4+ T-cell clone exhibits the phenotype of the helper T-cell clone (CD3+, CD4+, CD8-, WT31+) but suppresses the cytotoxic response of the autologous PBL in co-culture in the presence of the autologous tumor cells and exogenous IL-2. In some situations, these CD4+ suppressor T-cell clones exhibit considerable specificity for the autologous tumor cells. They do not suppress the cytotoxic response against allogeneic targets or against EBV-infected autologous lymphoblastoid cells. Furthermore, they specifically up-regulate their IL-2 receptors (IL-2R) when stimulated by the autologous tumor cells or with autologous tumor cell-pulsed antigen-presenting cells.(ABSTRACT TRUNCATED AT 400 WORDS)