title: The significance of low bcl-2 expression by CD45RO T cells in normal individuals and patients with acute viral infections. The role of apoptosis in T cell memory.
abstract: The bcl-2 gene product has been shown to prevent apoptotic cell death. We have now investigated the bcl-2 protein expression by resting and activated mature T cell populations. Freshly isolated CD45RO+ T cells within CD4+ and CD8+ subsets expressed significantly less bcl-2 than CD45RO- (CD45RA+) T cells (p < 0.001). When CD45RA+ T cells within both CD4+ and CD8+ subsets were activated in vitro, the transition to CD45RO phenotype was associated with a decrease in bcl-2 expression. Patients with acute viral infections such as infectious mononucleosis caused by Epstein-Barr virus infections or chickenpox, resulting from varicella zoster virus infection, had circulating populations of activated CD45RO+ T cells which also showed low bcl-2 expression. In these patients, a significant correlation was seen between low bcl-2 expression by activated T cells and their apoptosis in culture (r = 0.94, p < 0.001). These results suggest that the primary activation of T cells leads to the expansion of a population that is destined to perish unless rescued by some extrinsic event. Thus the suicide of CD45RO+ T cells could be prevented by the addition of interleukin 2 to the culture medium which resulted in a concomitant increase in the bcl-2 expression of these cells. Alternatively, apoptosis was also prevented by coculturing the activated T lymphocytes with fibroblasts, which maintained the viability of lymphoid cells in a restinglike state but with low bcl-2 expression. The paradox that the CD45RO+ population contains the primed/memory T cell pool yet expresses low bcl-2 and is susceptible to apoptosis can be reconciled by the observations that maintenance of T cell memory may be dependent on the continuous restimulation of T cells, which increases their bcl-2 expression. Furthermore, the propensity of CD45RO+ T cells to extravasate may facilitate encounter with fibroblast-like cells in tissue stroma and thus be an important additional factor which promotes the survival of selected primed/memory T cells in vivo.
authors.affiliation: Department of Clinical Immunology, Royal Free Hospital School of Medicine, London, UK.
authors.forename: A N
authors.initials: AN
authors.lastname: Akbar
authors.forename: N
authors.initials: N
authors.lastname: Borthwick
authors.forename: M
authors.initials: M
authors.lastname: Salmon
authors.forename: W
authors.initials: W
authors.lastname: Gombert
authors.forename: M
authors.initials: M
authors.lastname: Bofill
authors.forename: N
authors.initials: N
authors.lastname: Shamsadeen
authors.forename: D
authors.initials: D
authors.lastname: Pilling
authors.forename: S
authors.initials: S
authors.lastname: Pett
authors.forename: J E
authors.initials: JE
authors.lastname: Grundy
authors.forename: G
authors.initials: G
authors.lastname: Janossy
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology; D000208:Acute Disease; D000328:Adult; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D001706:Biopsy; D002478:Cells, Cultured; D002644:Chickenpox / Q000276:immunology; D005260:Female; D005347:Fibroblasts / Q000502:physiology; D006801:Humans; D007156:Immunologic Memory / Q000502:physiology*; D007244:Infectious Mononucleosis / Q000276:immunology; D007376:Interleukin-2 / Q000502:physiology; D017493:Leukocyte Common Antigens; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D014777:Virus Diseases / Q000276:immunology*
chemical_list: D007376:Interleukin-2; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011505:Protein-Tyrosine Kinases; D017493:Leukocyte Common Antigens