Try a new search

Format these results:

Searched for:



Total Results:


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

Shacklett BL; Beadle TJ; Pacheco PA; Grendell JH; Haslett PA; King AS; Ogg GS; Basuk PM; Nixon DF
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
PMID: 10954891
ISSN: 0889-2229
CID: 42912

Characterization of HIV-1-specific cytotoxic T lymphocytes expressing the mucosal lymphocyte integrin CD103 in rectal and duodenal lymphoid tissue of HIV-1-infected subjects

Shacklett BL; Beadle TJ; Pacheco PA; Grendell JH; Haslett PA; King AS; Ogg GS; Basuk PM; Nixon DF
Acute HIV-1 infection depletes CD4(+) T cells in gut-associated lymphoid tissue (GALT). The failure of containment of local viral replication, and consequent CD4(+) T cell depletion, might be due to delayed mobilization of effector CD8(+) T cells or absence of functioning HIV-1-specific CD8(+) T cell effectors within GALT. No studies have addressed human intestinal HIV-1-specific CD8(+) T cell functions. We sought to determine whether functional HIV-1-specific CTL were present in GALT and whether the repertoire differed from HIV-1-specific CTL isolated from peripheral blood mononuclear cells. From three HIV-1-infected subjects, we isolated HIV-1-specific CD8(+) T cells expressing the mucosal lymphocyte integrin CD103 from GALT. These antigen-specific effector cells could be expanded in vitro and lysed target cells in an MHC class I-restricted manner. HIV-1-specific CTL could be isolated from both duodenal and rectal GALT sites, indicating that CD8(+) effectors were widespread through GALT tissue. The breadth and antigenic specificities of GALT CTL appeared to differ from those in peripheral blood in some cases. In summary, we found HIV-1-specific CD8(+) effector T cells in GALT, despite HIV-1-induced CD4(+) T cell lymphopenia. This suggests that HIV-1-specific CTL in gut tissue can be maintained with limited CD4(+) T cell help
PMID: 10792991
ISSN: 0042-6822
CID: 42913