Phenotypic and functional characteristics of activated CD8+ cells: a CD11b-CD28- subset mediates noncytolytic functional suppression.
Freshly isolated human CD8+ cells can be divided into mutually exclusive subsets bearing the phenotypes CD11b+(CD28-) or CD28+(CD11b-). We found that activation of CD8+ cells with anti-CD3 mAb and IL-2 preferentially expanded the CD11b-(CD28+) subset. This subset, when separated and activated independently, mediated both functional suppression and lectin-dependent cell cytotoxicity (LDCC). CD28- cells, prepared by elimination of the CD 28+ cells from expanded unfractionated CD8+ cell cultures, retained functional suppressor activity but demonstrated reduced LDCC compared to either the CD28+(CD11b-)-enriched fraction or the unfractionated CD8+ population. The majority of the CD28- cells were also CD11b-, reflecting the observation that initially CD11b+ cells lose CD11b expression following activation with anti-CD3 mAb and IL-2. Our results therefore indicate that CD8+ cells deriving from the CD11b+CD28- subset, but expressing neither CD11b nor CD28 after activation, represent the main noncytotoxic functional suppressor cell in the mitogen "activated" suppressor assay. The preferential expansion of CD8+CD28+ cells relative to CD8+CD28- cells, if occurring in vivo in the central nervous system (CNS) compartment, would be consistent with observed phenotypic analysis of cerebrospinal fluid-derived T cells and might contribute to the reduced functional suppressor activity previously found for CNS compared to peripheral blood-derived lymphocytes.
Freedman
M S
MS
Department of Neurology & Neurosurgery, Montreal Neurological Institute, McGill University, Québec, Canada.
Ruijs
T C
TC
Blain
M
M
Antel
J P
JP
D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology* / Q000378:metabolism; D018106:CD28 Antigens; D016827:CD8 Antigens; D003602:Cytotoxicity, Immunologic / Q000187:drug effects / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D007165:Immunosuppression Therapy; D066298:In Vitro Techniques; D007694:Killer Cells, Natural / Q000502:physiology; D037102:Lectins / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000276:immunology*; D016177:Macrophage-1 Antigen / Q000378:metabolism; D011961:Receptors, Fc / Q000378:metabolism; D017452:Receptors, IgG; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000502:physiology
D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation; D000945:Antigens, Differentiation, T-Lymphocyte; D018106:CD28 Antigens; D016827:CD8 Antigens; D037102:Lectins; D016177:Macrophage-1 Antigen; D011961:Receptors, Fc; D017452:Receptors, IgG