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Reconstitution of T-cell function after CD6-depleted allogeneic bone marrow transplantation
| Content Provider | Scilit |
|---|---|
| Author | Soiffer, Rj Bosserman, L. Murray, C. Cochran, K. Daley, J. Ritz, J. |
| Copyright Year | 1990 |
| Abstract | Patients who undergo allogeneic bone marrow transplantation (BMT) are clinically immunodeficient for a prolonged period after engraftment. In the present study, we examined immune function after BMT in a series of patients who had received HLA compatible sibling marrow grafts purged of T cells with anti-CD6 monoclonal antibody and complement. None of the patients in this analysis received immunomodulating agents and none had developed graft-versus-host disease (GVHD). Initially after BMT, natural killer (NK) cells are the predominant cell type, giving way to CD3+, CD5+ T cells after 4 to 8 weeks. Despite the return of normal numbers of T lymphocytes post-BMT phenotypic analysis reveals several long-term abnormalities, including an inverted T4:T8 ratio and a significant fraction of CD3+ T cells that do not co-express CD6. In mitogenic assays, stimulation by either nonspecific lectin (phytohemagglutinin; PHA) or antibodies to the CD2 surface structure (anti-T11(2) + anti-T11(3)) results in decreased levels of T-cell proliferation compared with controls for over 18 months post-BMT. In contrast, the ability of unstimulated peripheral blood mononuclear cells (PBMC) to respond to recombinant interleukin-2 (rIL-2) is relatively intact, most likely reflecting early functional reconstitution of the NK cell population. To further characterize the prolonged abnormalities in T-cell proliferation after PHA or CD2 stimulation, we examined more proximal events in T-cell activation such as induction of IL-2 receptor expression and stimulus-induced intracellular calcium flux. We found that the induction of IL-2 receptor (p55) after in vitro activation, although initially abnormal, recovers completely by 6 months post-BMT. We also found that, after CD2 stimulation, calcium flux in T cells was normal immediately after engraftment. In contrast, after stimulation with anti-CD3 antibodies, a large population of T cells do not develop intracellular calcium flux compared with controls. We conclude that despite the recovery of normal numbers of T lymphocytes early after engraftment of CD6-depleted marrow, these T cells exhibit several physiologic and functional abnormalities that persist for varying intervals post-BMT. At present, it is unclear which of these specific defects is most closely associated with increased susceptibility to infectious agents after BMT. |
| Related Links | https://ashpublications.org/blood/article-pdf/75/10/2076/209651/2076.pdf |
| Ending Page | 2084 |
| Page Count | 9 |
| Starting Page | 2076 |
| DOI | 10.1182/blood.v75.10.2076.bloodjournal75102076 |
| Journal | Blood |
| Issue Number | 10 |
| Volume Number | 75 |
| Language | English |
| Publisher | American Society of Hematology |
| Publisher Date | 1990-05-15 |
| Access Restriction | Open |
| Subject Keyword | Hematology Antibodies Bone Marrow Lymphocytes Functional Bmt Normal Numbers Cd6 Depleted Compared with Controls Journal: Blood (Vol- 111, Issue- 10) |
| Content Type | Text |
| Resource Type | Article |
