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.

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.

• Authors: Su Jeong Ryu, Kyung Min Jung, Hyun Seung Yoo, Tae Woo Kim, Sol Kim, Jun Chang, Eun Young Choi
• Journal: Blood (Blood) Vol. 113 Issue 18 Pg. 4273-80 (Apr 30 2009) ISSN: 1528-0020 [Electronic] United States
• PMID: 19139082 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CD40 Antigens
• Minor Histocompatibility Antigens
• minor H antigen H60
• CD40 Ligand
• Interferon-gamma

Topics

• Adoptive Transfer
• Animals
• CD4-Positive T-Lymphocytes (immunology)
• CD40 Antigens (physiology)
• CD40 Ligand (physiology)
• CD8-Positive T-Lymphocytes (immunology)
• Cells, Cultured
• Cytotoxicity, Immunologic
• Female
• Flow Cytometry
• Graft Survival (immunology)
• Immunization
• Immunologic Memory (immunology)
• Interferon-gamma (metabolism)
• Lymphocyte Activation (physiology)
• Lymphocyte Culture Test, Mixed
• Lymphocyte Depletion
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Minor Histocompatibility Antigens (immunology)
• Skin Transplantation (immunology)
• Spleen (cytology, immunology, metabolism)