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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

Authors
Ryu, Su JeongJung, Kyung MinYoo, Hyun SeungKim, Tae WooKim, SolChang, JunChoi, Eun Young
Issue Date
30-Apr-2009
Publisher
AMER SOC HEMATOLOGY
Citation
BLOOD, v.113, no.18, pp.4273 - 4280
Indexed
SCIE
SCOPUS
Journal Title
BLOOD
Volume
113
Number
18
Start Page
4273
End Page
4280
URI
https://scholar.korea.ac.kr/handle/2021.sw.korea/120196
DOI
10.1182/blood-2008-09-181263
ISSN
0006-4971
Abstract
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. (Blood. 2009; 113: 4273-4280)
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