Please use this identifier to cite or link to this item:
https://ahro.austin.org.au/austinjspui/handle/1/9577
Title: | Generation and cytotoxic profile of human peripheral blood CD4+ T lymphocytes. | Austin Authors: | Smyth, Mark J | Affiliation: | Cellular Cytotoxicity Laboratory, Austin Research Institute, Austin Hospital, Heidelberg, Victoria, Australia | Issue Date: | 1-Dec-1992 | Publication information: | Immunology and Cell Biology; 70 ( Pt 6)(): 379-90 | Abstract: | The effects of a variety of metabolic and anti-tumour necrosis factor (TNF) antibodies were utilized to distinguish several different mechanisms of cytotoxicity employed by CD4+ effectors isolated from human peripheral blood lymphocytes (PBL). PBL, unseparated high buoyant density T cells and their CD4+ T cell subsets were activated with anti-CD3 monoclonal antibody (MoAb) and interleukin-2 (IL-2) for 1-5 days. CD4+ T cells activated with IL-2/anti-CD3 MoAb were cytotoxic when directed by a bispecific anti-nitrophenyl (NP)-anti-CD3 MoAb heteroconjugate against both NP-modified nucleated target cells (TC) and non-nucleated sheep red blood cells (SRBC). This CD4+ T population also lysed L929 in a TNF-alpha dependent manner. Interestingly, different mechanisms of nucleated and non-nucleated TC directed lysis by CD4+ effectors were implied by distinct patterns of sensitivity to cholera toxin (CT) and cyclosporin A (CsA). Cyclosporin A and CT inhibited CD4+ T cell directed lysis of SRBC, but not EL4. Cholera toxin, CsA or EGTA pretreatment also significantly inhibited the release of alpha-N-benzyloxycarbonyl-L-lysine-thiobenzylester (BLT)-esterase activity suggesting that degranulation of CD4+ effectors may be a critical step in their redirected lysis of SRBC. Overall, these findings suggested that activated human peripheral blood (PB) CD4+ effectors can lyse TC by at least three distinct mechanisms: (i) a CsA-sensitive directed lysis of SRBC which correlates with exocytosis and presumably occurs via membrane lesions; (ii) a CsA-insensitive directed lysis of NP-modified nucleated TC that does not appear to involve exocytosis and is metabolically distinct; and (iii) a direct TNF-dependent lysis of TNF-sensitive TC. The highly proliferative CD4+ T cell population could be propagated for at least 35 days while retaining cytotoxicity and secreting up to 80 U/mL of IL-2. These data raise the possibility that anti-CD3 MoAb plus IL-2 activated CD4+ T cells may prove effective in adoptive tumour immunotherapy. | Gov't Doc #: | 1363236 | URI: | https://ahro.austin.org.au/austinjspui/handle/1/9577 | DOI: | 10.1038/icb.1992.50 | Journal: | Immunology and cell biology | URL: | https://pubmed.ncbi.nlm.nih.gov/1363236 | Type: | Journal Article | Subjects: | Antibody Specificity Antimetabolites.pharmacology Biological Markers CD4-Positive T-Lymphocytes.drug effects.immunology Cell Division Cells, Cultured Cytotoxicity, Immunologic.drug effects Exocytosis Humans Killer Cells, Natural.drug effects.immunology Lymphokines.secretion T-Lymphocytes, Helper-Inducer.drug effects.immunology Tumor Cells, Cultured |
Appears in Collections: | Journal articles |
Show full item record
Items in AHRO are protected by copyright, with all rights reserved, unless otherwise indicated.