T cell clones expressing the natural killer cell-related p58 receptor molecule display heterogeneity in phenotypic properties and p58 function.
A new anti-p58 monoclonal antibody (mAb), termed CH-L, has been used to characterize a minor subset of T lymphocytes co-expressing p58 and CD3 molecules. In two-color immunofluorescence analysis, CH-L+CD3+ cells represented 0.5 to 6% of the peripheral blood lymphocytes (in 20 healthy donors). Clonal analysis showed that most CD3+CH-L+ T cell clones expressed the CD8+4- T cell receptor (TcR) alpha/beta+ phenotype, while only a few were CD8-4+ TcR alpha/beta, CD8-4- TcR alpha/beta+ or CD8-4- TcR gamma/delta+. Western blot analysis indicated that the CH-L mAb identifies the same 56-58-kDa diffuse band in both T and natural killer cell (NK) clones. A minority of T cell clones also expressed other NK-related markers such as CD16, CD56 and CD94 and two clones also reacted with the anti-p58 mAb EB6. Interestingly, most clones displayed cytolytic activity in an anti-CD3 mAb-triggered redirected killing assay against the Fc gamma receptor+ P815 target cells and NK-like activity against K562 and Raji cells. In contrast, the IGROV-1 ovarian carcinoma cell line was resistant to cytolysis by all of these clones. Since p58 molecules have previously been shown to exert regulatory functions on NK-mediated lysis, we investigated whether anti-p58 mAb could also influence cytotoxicity mediated by CD3+p58+ T lymphocytes. Lysis of P815 target cells, triggered by anti-CD3 mAb, could be inhibited by anti-p58 mAb in 8 out of 12 cytolytic clones tested, while 4 clones were not inhibited. In addition, anti-p58 mAb enhanced the cytolytic activity of 3 clones against IGROV-1 and of 4 other clones against Raji target cells. Taken together, these data indicate that p58+ T cells express heterogeneous phenotypes and different forms of TcR and, in most instances, display cytolytic functions. Perhaps more importantly, the p58 molecule appears to modulate the cytolytic activity triggered via the CD3/TcR complex.
Ferrini
S
S
Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
Cambiaggi
A
A
Meazza
R
R
Sforzini
S
S
Marciano
S
S
Mingari
M C
MC
Moretta
L
L
D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D017252:CD3 Complex / Q000032:analysis; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007111:Immunity, Cellular; D007694:Killer Cells, Natural / Q000276:immunology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000276:immunology*; D011971:Receptors, Immunologic / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D000097682:Lamin B Receptor
D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D018160:Receptors, Cytoplasmic and Nuclear; D011971:Receptors, Immunologic; D000097682:Lamin B Receptor