Abstract

Dissection of mature human T cells into those that mediate predominantly helper/inducer effects (Leu 3, T4) and those that mediate predominantly suppressor/cytotoxic effects (Leu 2, T8) was made possible with monoclonal antibodies. Using the mixed leukocyte reaction (MLR) as a model system, we have further fractionated these two major T lineages into subsets with relatively narrow functional repetoires. For example, immunoglobulin synthesis induced in MLR was shown to be regulated by sequential interactions between subsets of Leu 2?-?,3?+? suppressor inducer cells, Leu 2?+?,3?-?DR?+? suppressor-amplifier cells, and Leu 2?+?,3?-?,DR?-? suppressor-effector cells. We further showed that Leu 3?+? cells capable of helping B cell differentiation and Ig synthesis can be distinguished from Leu 3?+? cells that do not provide help on the basis of their expression of the Leu 8 marker. Finally, precursors of Leu 2 suppressor-effector cells (Ts) were distinguished from precursors of Leu 2?+? cytotoxic cells on the basis of their differential expression of the 9.3 antigen. In summary, these data indicate that human T lymphocytes consist of a larger number of functionally distinct subsets than heretofore recognized, distinguishable from one another with combinations of monoclonal antibodies directed at cell surface markers. (LB)

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37CA024607-16
Application #
2087273
Study Section
Special Emphasis Panel (NSS)
Project Start
1979-01-01
Project End
1995-12-31
Budget Start
1994-01-01
Budget End
1994-12-31
Support Year
16
Fiscal Year
1994
Total Cost
Indirect Cost

  Institution

Name
Stanford University
Department
Pathology
Type
Schools of Medicine
DUNS #
800771545
City
Stanford
State
CA
Country
United States
Zip Code
94305

  Publications

Kos, F J; Engleman, E G (1996) Immune regulation: a critical link between NK cells and CTLs. Immunol Today 17:174-6
Ruegg, C L; Wu, H Y; Fagnoni, F F et al. (1996) B4B, a novel growth-arrest gene, is expressed by a subset of progenitor/pre-B lymphocytes negative for cytoplasmic mu-chain. J Immunol 157:72-80
Rivas, A; Ruegg, C L; Zeitung, J et al. (1995) V7, a novel leukocyte surface protein that participates in T cell activation. I. Tissue distribution and functional studies. J Immunol 154:4423-33
Ruegg, C L; Rivas, A; Madani, N D et al. (1995) V7, a novel leukocyte surface protein that participates in T cell activation. II. Molecular cloning and characterization of the V7 gene. J Immunol 154:4434-43
Takamizawa, M; Fagnoni, F; Mehta-Damani, A et al. (1995) Cellular and molecular basis of human gamma delta T cell activation. Role of accessory molecules in alloactivation. J Clin Invest 95:296-303
Kos, F J; Engleman, E G (1995) Requirement for natural killer cells in the induction of cytotoxic T cells. J Immunol 155:578-84
Sansoni, P; Passeri, G; Fagnoni, F et al. (1995) Inhibition of antigen-presenting cell function by alendronate in vitro. J Bone Miner Res 10:1719-25
Godfrey, W R; Fagnoni, F F; Harara, M A et al. (1994) Identification of a human OX-40 ligand, a costimulator of CD4+ T cells with homology to tumor necrosis factor. J Exp Med 180:757-62
Mohagheghpour, N; Bermudez, L E; Khajavi, S et al. (1992) The VLA-4/VCAM-1 molecules participate in gamma delta cell interaction with endothelial cells. Cell Immunol 143:170-82
Suzuki, T; Suzuki, N; Daynes, R A et al. (1991) Dehydroepiandrosterone enhances IL2 production and cytotoxic effector function of human T cells. Clin Immunol Immunopathol 61:202-11

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