Frequency, specificity, and phenotype of clonally growing human alloreactive interleukin-2-secreting helper T lymphocyte precursors.
Limiting dilution cultures were performed to detect allospecific IL-2-secreting helper T lymphocyte precursors (HTL-p) among human peripheral blood mononuclear cells, E-rosette-purified (E+) and cell-sorter-separated CD4+/8- as well as CD4-/8+ T cell subsets. Split-well cultures were set up prior to restimulation to assess the antigen specificity of the response. Frequencies of alloreactive IL-2-secreting HTL-p in fully HLA-mismatched responder/stimulator cell combinations ranged from 1/200 to 1/900 (among PBMNC), from 1/50 to 1/301 (among E+ T cells), from 1/36 to 1/220 (among CD4+ T cells), and from 1/38 to 1/450 (among CD8+ T cells). Allospecificity of effector T cells was demonstrated by a strong decline of frequencies obtained after restimulation against unrelated third-party antigens. In clonal segregation analysis, the vast majority of IL-2-secreting progeny (80-90%) were exclusively specific for the original stimulating alloantigen. Finally, the allele specificity of human alloreactive HTL-p was revealed by comparing frequency estimates obtained after restimulation with partially identical stimulator/third-party antigen combinations.
Theobald
M
M
Department of Internal Medicine III, Ulm University Hospital, Federal Republic of Germany.
Hoffmann
T
T
Bunjes
D
D
Heit
W
W
D000483:Alleles; D015703:Antigens, CD / Q000502:physiology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology; D015704:CD4 Antigens / Q000502:physiology; D016827:CD8 Antigens; D002999:Clone Cells; D006680:HLA Antigens / Q000235:genetics; D006801:Humans; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000378:metabolism*; D007519:Isoantigens / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D012397:Rosette Formation; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D015704:CD4 Antigens; D016827:CD8 Antigens; D006680:HLA Antigens; D007376:Interleukin-2; D007519:Isoantigens