title: Differences in surface phenotype between cytolytic and non-cytolytic CD4+ T cells. MHC class II-specific cytotoxic T lymphocytes lack Leu 8 antigen and express CD2 in high density.
abstract: A number of cell surface molecules are differentially expressed on functionally distinct subsets of CD4+ T cells. However, to date CD4+ T cells capable of becoming CTL have not been shown to be phenotypically distinct from other CD4+ T cells, and in the current study we examined the ability of Leu 8+ and Leu 8- CD4+ subpopulations to become cytotoxic effectors after their stimulation with allogeneic lymphoblastoid cell lines. Although CD4+, Leu 8+ cells proliferated more vigorously than CD4+, Leu 8- cells in primary cultures stimulated with allogeneic LCL, the CD4+, Leu 8- population was the major source of cytotoxic effectors, killing targets with specificity for their class II MHC alloantigens. In most subjects, CD4+ precursors of CTL were distinguished not only by their lack of Leu 8 expression but also by their relatively high density of CD2, LFA-1, and LFA-3, molecules known to mediate non-specific cell-to-cell adhesion and postulated to be markers of immunologic memory. The absence of Leu 8 does not appear to be a reliable memory cell marker, however, because Leu 8+ as well as Leu 8-, CD4+ cells from PPD skin test positive subjects responded to the recall Ag, PPD. During 3 mo of continuous culture with allogeneic stimulators, Leu 8- cells retained their cytolytic activity and remained unreactive with anti-Leu 8 mAb, whereas Leu 8+ cells remained non-cytolytic and reactive with anti-Leu 8, suggesting that under the conditions used the Leu 8 phenotype is relatively stable. PHA or anti-CD3 mAb enhanced non-specific killing by alloantigen-stimulated CD4+,Leu 8- lines but failed to unmask any cytolytic potential in CD4+,Leu 8+ lines. We conclude that MHC class II-specific cytolytic CD4+ T cells can be distinguished from non-cytolytic CD4+ cells on the basis of their surface phenotype, and that most CD4+ CTL are contained within the Leu 8- subpopulation.
authors: Department of Pathology, Stanford University School of Medicine, CA 94305.
authors: S
authors: S
authors: Takada
authors: J
authors: J
authors: Koide
authors: E G
authors: EG
authors: Engleman
mesh_terms: D000818:Animals; D000943:Antigens, Differentiation / Q000032:analysis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis*; D000954:Antigens, Surface / Q000032:analysis; D018801:CD2 Antigens; D003602:Cytotoxicity, Immunologic; D000939:Epitopes / Q000032:analysis; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D007519:Isoantigens / Q000276:immunology; D007958:Leukocyte Count; D008213:Lymphocyte Activation; D051379:Mice; D010641:Phenotype; D011971:Receptors, Immunologic / Q000032:analysis*; D013602:T-Lymphocytes, Cytotoxic / Q000145:classification* / Q000276:immunology
chemical_list: D000943:Antigens, Differentiation; D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D018801:CD2 Antigens; D000939:Epitopes; D000949:Histocompatibility Antigens Class II; D007519:Isoantigens; D011971:Receptors, Immunologic