Journal of Applied Sciences & Environmental Management,
Vol. 8, No. 1, June, 2004, pp. 55-56
Adoptive immunotherapy for cytomegalovirus infection
Kei Numazaki, M D
Department of Pediatrics, Sapporo
Medical University School of Medicine, S.1 W.16 Chuo-ku, Sapporo, 060-8543 Japan
Code
Number: ja04011
ABSTRACT:
We reported a case with interstitial pneumonia
associated with cytomegalovirus (CMV) infection in whom clinical improvement
was observed after the treatment with primary adoptive immunotherapy. Although
adoptive transfer of CMV-specific T cells offers the potential for reconstitution
of viral immunity after allegoric transplantation, the logistics of producing
virus-specific T-cell clones has limited the application of therapies.
@JASEM
Under
immunosuppressive conditions, latent or persistent cytomegalovirus (CMV)
infection can be reactivated to produce a wide variety of clinical manifestations. Unfortunately,
no successful antiviral treatment of pediatric CMV infection without displaying
cytotoxicity has yet been developed. Adoptive transfer of antigen-specific
cytotoxic T lymphocytes (CTLs) offers safe and effective therapy for certain
viral infections.
Peggs and colleagues (2003) reported that they treated patients
for CMV infection with polyclonal CMV-specific T-cell lines and that massive
in-vivo expansions of CMV-specific cytotoxic T lymphocytes were observed,
resulting in reconstitution of viral immunity.
MATERIALS AND METHODS
We reported a case with interstitial pneumonia associated with CMV infection
in whom clinical improvement was observed after the treatment with primary
adoptive immunotherapy (Numazaki et al., 1997). A 17-month-old
girl was admitted because of cough and dyspnea. Her chest roentgenogram
demonstrated interstitial pneumonic shadow. At this time serum IgG and IgM
antibodies against CMV were detected and CMV was isolated from sputum and
urine. CMV DNA was also detected from her peripheral blood mononuclear cells
(PBMCs) by PCR.
Her PBMCs were separated from blood and cultured with immobilized anti-CD3
monoclonal antibody and human recombinant interleukin 2 (rIL-2).
A rapid proliferation of T lymphocytes was obtained by this procedure. Cultured
T lymphocytes were then transferred to a gas-permeable culture bag and culture
continued for an additional 8 days with an increasing volume of medium. T
cell numbers increased about 2000-hold during 2 weeks of culture. The final
population contained about 30% CD4+ and 60% CD8+ T lymphocytes. CD4+ T lymphocytes
had cytotoxic activity as strong as CD8+ cells. T lymphocytes generated
from her peripheral blood were administered intravenously to the patient
in six doses (4.3x108 to 1.1x109 cells)
of a total of 4.03x1010 cells.
RESULTS
AND DISCUSSIONS
After the treatment with primary adoptive immunotherapy, chest radiograph showed
resolution of infiltrates, CMV was not isolated from sputum and CMV DNA was
not detected from PBMCs. Clinical symptoms and laboratory abnormal findings
improved and CMV disappeared from clinical specimens after the treatment
with primary adoptive immunotherapy. The virus-specific CD8+ cytotoxic and
CD4+ helper or cytotoxic T cells may be amplified and used to control CMV
infection.
Walter and colleagues (1995) provides important evidence that
infusion of donor-derived CD8+ cytotoxic T-cell clones specific for CMV can
promptly reconstitute cellular immunity against CMV in recipients of allogenic
bone marrow, thus reducing the risk of morbidity and mortality related to
viral infection. However, the persistence of transferred CD8+ cytotoxic
cells was prompted by the recovery of the response of CD4+ CMV-specific helper
T cells.
The infusion of virus-specific polyclonal T-cell lines containing both CD4+
and CD8+ cells has been successfully used to control infection with Epstein-Barr
virus (EBV) and related lymphoproliferative disorders of recipients of allogenic
bone marrow (Rooney et al., 1995).
Locatelli and colleagues (1996)
suggested that donor-derived polyclonal T-cell lines enriched with CMV-reactive
T cells might be also useful for the reconstitution of immunity.
As Peggs and colleagues (2003) report, although adoptive transfer
of CMV-specific T cells offers the potential for reconstitution of viral
immunity after allegoric transplantation, the logistics of producing virus-specific
T-cell clones has limited the application of therapies.