Differential recovery of phenotypically and functionally distinct circulating antigen-presenting cells after allogeneic marrow transplantation.
Low-density cells (LDC) prepared from peripheral blood by fractionation over hypertonic metrizamide contain 95% of cells with veiled morphology, almost all of which are HLA-DR-positive and have characteristics of antigen-presenting cells. In normal individuals the monoclonal antibodies RFD1 and RFD2 divide these cells into three phenotypically distinct populations, D1+D2-, D1-D2+ and D1-D2-. The RFD1-positive population is nonphagocytic. We have investigated the recovery of LDC in peripheral blood after (T cell-depleted) marrow transplantation, to assess whether defects in antigen-presenting cell (APC) subpopulations could contribute to the prolonged immune-paresis of marrow graft recipients. We find that APC of donor origin and with apparently normal morphology, phenotype, and function appear within 6 weeks of BMT. By three months the donor-derived nonphagocytic RFD1-positive subset has disappeared, although phagocytic RFD2-positive cells remain. The disappearance of the RFD1-positive subset is associated with a loss of antigen presentation by patients' LDC of the soluble protein antigen tetanus toxoid, though the capacity to present alloantigen and stimulate in a mixed lymphocyte reaction is retained. Donor-derived RFD1-positive cells and soluble antigen-presenting capacity do not reappear for one year or more. This biphasic recovery of RFD1-positive cells contrasted with the continued production of RFD2-positive APC, implies that the phenotypic and functional distinction between APC subpopulations in peripheral blood also reflects a separate ontogeny. Since these marrow graft recipients retain the phagocytic (RFD2-positive) APC but lose the nonphagocytic (RFD1-positive) APC subset, there is now an opportunity to explore the role of each subset in antigen processing and presentation.
Reittie
J E
JE
Department of Haematology, Royal Free Hospital, Hampstead, London.
Poulter
L W
LW
Prentice
H G
HG
Burns
J
J
Drexler
H G
HG
Balfour
B
B
Clarke
J
J
Hoffbrand
A V
AV
McGee
J O
JO
Brenner
M K
MK
D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal; D000938:Antigen-Presenting Cells / Q000145:classification* / Q000166:cytology / Q000276:immunology; D016026:Bone Marrow Transplantation; D002452:Cell Count; D002648:Child; D005260:Female; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D008137:Longitudinal Studies; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D010641:Phenotype; D013745:Tetanus Toxoid / Q000276:immunology; D014019:Tissue Donors; D014184:Transplantation, Homologous
D000911:Antibodies, Monoclonal; D006684:HLA-DR Antigens; D013745:Tetanus Toxoid