Isolation of cytomegalovirus-specific cytotoxic T-lymphocytes from gut-associated lymphoid tissue (GALT) of HIV type 1-infected subjects

T. J. Beadle, Barbara Shacklett, P. A. Pacheco, J. H. Grendell, P. A J Haslett, A. S. King, G. S. Ogg, P. M. Basuk, D. F. Nixon

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Cytomegalovirus (CMV) can be an important opportunistic infection in HIV-1-infected patients, particularly when the CD4+ T-cell count drops below 50 lymphocytes/mm3. CMV-associated disease, including retinitis, pneumonitis, gastroenteritis, and encephalitis, is estimated to affect up to 40% of AIDS patients. We have studied the cellular immune response to CMV in gut-associated lymphoid tissue (GALT) of HIV-1-infected patients. Two patients with chronic diarrhea of unknown etiology were examined by flexible sigmoidoscopy and upper endoscopy. Biopsy specimens were obtained from lymphoid-associated tissue sites in rectum and duodenum. Both patients were seropositive for CMV IgG, but had not been treated with ganciclovir, and neither had clinical signs of CMV disease. Mononuclear cell cultures were established from GALT and blood and assayed for the presence of CMV-specific CD8+ T cells. CD8+ T-cell phenotype and function were assessed by MHC Class I tetramer staining, using an HLA-A*0201 tetramer complex specific for peptide 495-503 (NLVPMVATV) of CMV lower matrix protein pp65, and by a standard 51Cr release assay. CMV pp65-specific cytotoxic lymphocytes (CTL) were detected in GALT and blood MNC from both patients. These results demonstrate that HIV-1-infected subjects seropositive for CMV, but without active CMV gastrointestinal disease, harbor CMV-specific CTL in intestinal lymphoid tissue. This is the first report of isolation of CMV-specific CTL in GALT and will lead to greater understanding of the pathogenesis of CMV disease in human mucosal tissue.

Original languageEnglish (US)
Pages (from-to)1157-1162
Number of pages6
JournalAIDS Research and Human Retroviruses
Volume16
Issue number12
DOIs
StatePublished - Aug 10 2000
Externally publishedYes

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Cytotoxic T-Lymphocytes
Lymphoid Tissue
Cytomegalovirus
HIV-1
Lymphocytes
T-Lymphocytes
Retinitis
Sigmoidoscopy
Ganciclovir
Gastrointestinal Diseases
Opportunistic Infections
Gastroenteritis
Encephalitis
CD4 Lymphocyte Count
Duodenum
Rectum
Cellular Immunity
Endoscopy
Diarrhea
Pneumonia

ASJC Scopus subject areas

  • Immunology
  • Virology

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Isolation of cytomegalovirus-specific cytotoxic T-lymphocytes from gut-associated lymphoid tissue (GALT) of HIV type 1-infected subjects. / Beadle, T. J.; Shacklett, Barbara; Pacheco, P. A.; Grendell, J. H.; Haslett, P. A J; King, A. S.; Ogg, G. S.; Basuk, P. M.; Nixon, D. F.

In: AIDS Research and Human Retroviruses, Vol. 16, No. 12, 10.08.2000, p. 1157-1162.

Research output: Contribution to journalArticle

Beadle, T. J. ; Shacklett, Barbara ; Pacheco, P. A. ; Grendell, J. H. ; Haslett, P. A J ; King, A. S. ; Ogg, G. S. ; Basuk, P. M. ; Nixon, D. F. / Isolation of cytomegalovirus-specific cytotoxic T-lymphocytes from gut-associated lymphoid tissue (GALT) of HIV type 1-infected subjects. In: AIDS Research and Human Retroviruses. 2000 ; Vol. 16, No. 12. pp. 1157-1162.
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AU - Grendell, J. H.

AU - Haslett, P. A J

AU - King, A. S.

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AU - Basuk, P. M.

AU - Nixon, D. F.

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AB - Cytomegalovirus (CMV) can be an important opportunistic infection in HIV-1-infected patients, particularly when the CD4+ T-cell count drops below 50 lymphocytes/mm3. CMV-associated disease, including retinitis, pneumonitis, gastroenteritis, and encephalitis, is estimated to affect up to 40% of AIDS patients. We have studied the cellular immune response to CMV in gut-associated lymphoid tissue (GALT) of HIV-1-infected patients. Two patients with chronic diarrhea of unknown etiology were examined by flexible sigmoidoscopy and upper endoscopy. Biopsy specimens were obtained from lymphoid-associated tissue sites in rectum and duodenum. Both patients were seropositive for CMV IgG, but had not been treated with ganciclovir, and neither had clinical signs of CMV disease. Mononuclear cell cultures were established from GALT and blood and assayed for the presence of CMV-specific CD8+ T cells. CD8+ T-cell phenotype and function were assessed by MHC Class I tetramer staining, using an HLA-A*0201 tetramer complex specific for peptide 495-503 (NLVPMVATV) of CMV lower matrix protein pp65, and by a standard 51Cr release assay. CMV pp65-specific cytotoxic lymphocytes (CTL) were detected in GALT and blood MNC from both patients. These results demonstrate that HIV-1-infected subjects seropositive for CMV, but without active CMV gastrointestinal disease, harbor CMV-specific CTL in intestinal lymphoid tissue. This is the first report of isolation of CMV-specific CTL in GALT and will lead to greater understanding of the pathogenesis of CMV disease in human mucosal tissue.

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