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Reconstitution of T-cell function after CD6-depleted allogeneic bone marrow
transplantation
RJ Soiffer, L Bosserman, C Murray, K Cochran, J Daley and J Ritz
Division of Tumor Immunology, Dana-Farber Cancer Institute, Boston, MA
02115.
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.
Volume 75,
Issue 10,
pp. 2076-2084,
05/15/1990
Copyright © 1990 by The American Society of Hematology
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