| First Author | Ryu SJ | Year | 2009 |
| Journal | Blood | Volume | 113 |
| Issue | 18 | Pages | 4273-80 |
| PubMed ID | 19139082 | Mgi Jnum | J:148435 |
| Mgi Id | MGI:3844788 | Doi | 10.1182/blood-2008-09-181263 |
| Citation | Ryu SJ, et al. (2009) Cognate CD4 help is essential for the reactivation and expansion of CD8 memory T cells directed against the hematopoietic cell-specific dominant minor histocompatibility antigen, H60. Blood 113(18):4273-80 |
| abstractText | In contrast to previous notions of the help-independency of memory CD8 T cells during secondary expansion, here we show that CD4 help is indispensable for the re-expansion of once-helped memory CD8 T cells, using a hematopoietic cell-specific dominant minor histocompatibility (H) antigen, H60, as a model antigen. H60-specific memory CD8 T cells generated during a helped primary response vigorously expanded only when rechallenged under helped conditions. The help requirement for an optimal secondary response was confirmed by a reduction in peak size by CD4 depletion, and was reproduced after skin transplantation. Helpless conditions or noncognate separate help during the secondary response resulted in a significant reduction in the peak size and different response kinetics. Providing CD4 help again during a tertiary challenge restored robust memory expansion; however, the repeated deprivation of help further reduced clonal expansion. Adoptively transferred memory CD8 T cells did not proliferate in CD40L(-/-) hosts. In the CD40(-/-) hosts, marginal memory expansion was detected after priming with male H60 cells but was completely abolished by priming with peptide-loaded CD40(-/-) cells, suggesting the essential role of CD40 and CD40L in memory responses. These results provide insight into the control of minor H antigen-specific CD8 T-cell responses, to maximize the graft-versus-leukemia response. |
