Submitted September 29, 2008
Accepted December 25, 2008
Cognate CD4 help is essential for the reactivation and expansion of CD8 memory T cells directed against the haematopoietic cell-specific dominant minor histocompatibility antigen, H60
Su Jeong Ryu, Kyung Min Jung, Hyun Seung Yoo, Tae Woo Kim, Sol Kim, Jun Chang, and Eun Young Choi*
Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea, Republic of
Graduate Program of Immunology, Seoul National University College of Medicine, Seoul, Korea, Republic of
Graduate School of Medicine, Korea University, Seoul, Korea, Republic of
Division of Life and Pharmaceutical Sciences, Ewha Womans University, Seoul, Korea, Republic of
* Corresponding author; email: eycii{at}snu.ac.kr.
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 haematopoietic 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 re-challenged 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 non-cognate separate-help during the secondary response resulted in a significant reduction in the peak size and different response kinetics. Re-providing CD4 help 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.
