Lymphokine production by T-cell clones after human bone marrow transplantation.
T cells recovering after bone marrow transplantation (BMT) were analyzed for their phenotypic and functional features by two-color immunofluorescence and a high efficiency cloning technique. A predominance of cells co-expressing natural killer (NK)-related surface antigens, such as Leu 7 (CD57) and CD11b, was detected within both the CD4+ and CD8+ subsets from 5 months postgrafting onward. Such cells are virtually absent among normal circulating CD4+ cells and account for a minority (approximately 30%) of normal CD8+ cells. Postgrafting T cells representative of the whole range of NK-related antigen co-expression were selected from six patients for clonal analyses. In control subjects, 63% and 41% of the CD4+ and CD8+ clones, respectively, produced interleukin-2 (IL-2) whereas approximately 30% of either CD4+ or CD8+ control clones produced interferon (IFN)-gamma. At variance, and irrespective of their CD4+/CD8+ phenotype, lower proportions of BMT recipient-derived clones produced IL-2 (20% and 12%, respectively), whereas the majority of both CD4+ and CD8+ clones (75% and 71%, respectively) released high amounts of IFN-gamma. Purified populations of CD57+/CD11b+ v negative cells from two BMT recipients and two control subjects were cloned and subsequently evaluated for IL-2 and IFN-gamma production. CD57+/CD11b+ cell-derived clones were poor IL-2 producers in both normal subjects and BMT patients. In contrast, IL-2-producing clones were frequent (62% to 79%) among those derived from CD57-/CD11b- cells from normal subjects, whereas they were still represented at lower than normal proportions, ie, 25% to 41%, among clones generated from BMT recipients. CD57+/CD11b+ cells gave rise to comparably high proportions of IFN-gamma producing clones in both normal subjects and BMT recipients (approximately 80%). In contrast, IFN-gamma producing clones were approximately 25% to 50% of CD57-/CD11b- cell-derived clones in both normal subjects and BMT patients. Therefore, while the predominance of NK-related antigen-positive T cells may be predictive of poor IL-2 and high IFN-gamma production, the immune derangement in long-term BMT recipients is further enhanced by the finding that all T cells may be poor IL-2 producers. It is also suggested that IL-2 production is a preferential function of T cells that do not express CD57 and CD11b, whereas IFN-gamma production is attributable to T cells that express CD57 and CD11b.
Velardi
A
A
Department of Medicine, University of Perugia, Italy.
Varese
P
P
Terenzi
A
A
Dembech
C
C
Albi
N
N
Grossi
C E
CE
Moretta
L
L
Martelli
M F
MF
Grignani
F
F
Mingari
M C
MC
D015703:Antigens, CD / Q000032:analysis; D016026:Bone Marrow Transplantation; D002478:Cells, Cultured; D002999:Clone Cells; D005455:Fluorescent Antibody Technique; D006801:Humans; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000096:biosynthesis*; D007376:Interleukin-2 / Q000096:biosynthesis*; D007694:Killer Cells, Natural / Q000276:immunology; D007700:Kinetics; D010641:Phenotype; D013601:T-Lymphocytes / Q000276:immunology*
D015703:Antigens, CD; D007376:Interleukin-2; D007371:Interferon-gamma