| First Author | Berger DP | Year | 2000 |
| Journal | Virology | Volume | 266 |
| Issue | 2 | Pages | 257-63 |
| PubMed ID | 10639312 | Mgi Jnum | J:59946 |
| Mgi Id | MGI:1352328 | Doi | 10.1006/viro.1999.0074 |
| Citation | Berger DP, et al. (2000) Defining parameters for successful immunocytotherapy of persistent viral infection. Virology 266(2):257-63 |
| abstractText | Persistent infections with viruses such as HIV, Epstein-Barr virus, cytomelagovirus, and hepatitis B and C viruses continue to be major human health problems. Immunocytotherapy for persistent viral infections has proven successful in animal models but less effective in humans. While the requirement of antigen-specific CD8(+) T cells is known, the precise role of CD4(+) T cells as regards specific priming, numbers needed, and interaction with CD8(+) T cells is less clear. To address these issues, we used a mouse model of persistent virus infection in which adoptive transfer of T cells effectively purges virus from all tissues. We demonstrate that (1) inclusion of antigen-specific CD4(+) in addition to CD8(+) T cells is mandatory for efficient and long-term virus control. Neither naive nor CD4(+) T cells with specificity for a different virus are sufficient. (2) The minimal numbers of virus-specific T cells required for virus clearance from sera and tissues are 350,000 virus-specific CD8(+) and 7000 virus-specific CD4(+) T cells or approximately 5 x 10(7) CD8(+) and as few as 1 x 10(6) CD4(+) T cells per square meter of body surface area, a CD8:CD4 ratio of 50:1. (3) Production of interferon-gamma, obligatory for resolution of persistent infection, is dependent on the interaction of virus-specific CD4(+) and CD8(+) T cells. (4) Maintenance of CD8(+) T cell effector functions after adoptive transfer is directly proportional to the amount of cotransferred, virus-specific CD4(+) T cells. Copyright 2000 Academic Press. |
