ABSTRACT
CD8+ T cells employ granzyme B (GrB) to induce apoptosis in target cells. Increased expression of GrB has been put forward as a diagnostic marker in transplant rejection and viral infection. Three-color flow cytometric analysis revealed that peripheral blood CD8+ T lymphocytosis during primary cytomegalovirus infection after renal transplantation resulted from expansion of a CD8+GrB+CD62L+ T cell subset that was almost absent during stable transplant function or acute rejection. This expansion coincided with a temporary increase in systemic soluble GrB (sGrB) levels. No such increase was observed during stable transplant function or acute rejection. Thus, the primary immune response to cytomegalovirus infection is accompanied by appearance of CD8+GrB+CD62L+ T cells and increased sGrB levels in the peripheral blood compartment. Determination of the latter may provide a novel approach for monitoring viral infections.
Subject(s)
CD8-Positive T-Lymphocytes/enzymology , Cytomegalovirus Infections/immunology , Kidney Transplantation , Postoperative Complications , Serine Endopeptidases/blood , Adolescent , Adult , CD8-Positive T-Lymphocytes/immunology , Child , Cytomegalovirus Infections/blood , Cytomegalovirus Infections/enzymology , Female , Flow Cytometry , Granzymes , Humans , L-Selectin/blood , Male , Middle Aged , Prospective Studies , Serine Endopeptidases/biosynthesisSubject(s)
Cytomegalovirus Infections/blood , Kidney Transplantation/physiology , Serine Endopeptidases/blood , Adult , Cytomegalovirus Infections/immunology , Cytotoxicity, Immunologic , Enzyme-Linked Immunosorbent Assay , Female , Follow-Up Studies , Granzymes , Humans , Kidney Transplantation/immunology , Longitudinal Studies , Male , Middle Aged , Postoperative Complications , Retrospective Studies , Time FactorsSubject(s)
CD8-Positive T-Lymphocytes/immunology , Cytomegalovirus Infections/immunology , Herpesviridae Infections/immunology , Immunologic Memory , Kidney Transplantation/immunology , L-Selectin/blood , Postoperative Complications , Serine Endopeptidases/blood , Adult , Antigens, CD/blood , Cyclosporine/therapeutic use , Female , Granzymes , HLA-DR Antigens/blood , Herpesvirus 4, Human , Humans , Immunosuppressive Agents/therapeutic use , Kidney Transplantation/physiology , Male , Middle Aged , Prednisolone/therapeutic use , Receptors, Interleukin-2/blood , T-Lymphocyte Subsets/immunology , Transplantation, HomologousABSTRACT
Granzyme B (GrB) has been implicated in induction of apoptosis in target cells. The presence of GrB in peripheral blood CD8+ T cells from healthy individuals was analysed in immunocytochemical and flow cytometric studies. Furthermore, CD8+ GrB- T cells and CD8+ GrB+ T cells were compared regarding phenotypical characteristics and susceptibility to both spontaneous and Fasmediated apoptosis. GrB was expressed by approximately one-fifth of CD8+ T cells. Compared with the CD8+ GrB- T-cell subset, the CD8+ GrB+ T-cell subset contained cells that were relatively more activated and more prone to spontaneous apoptosis. Culturing of cells with immunoglobulin M (IgM) anti-Fas monoclonal antibody had no additional effect on the number of CD8+ GrB+ T cells undergoing apoptosis. We suggest that the presence of CD8+ GrB+ T cells in peripheral blood from healthy individuals results from immune surveillance or contact with infectious agents, and that spontaneous apoptosis of these cells might serve as a mechanism for their eventual clearance.
