Dominant human CD8 T cell clonotypes persist simultaneously as memory and effector cells in memory phase.

Abstract

The adaptive immune system plays a critical role in protection at the time of secondary infection. It does so through the rapid and robust reactivation of memory T cells which are maintained long-term, in a phenotypically heterogeneous state, following their primary encounter with Ag. Although most HLA-A*0201/influenza matrix protein(58-66)-specific CD8 T cells from healthy donors display characteristics typical of memory T cells, through our extensive phenotypic analysis we have further shown that up to 20% of these cells express neither the IL-7 receptor CD127 nor the costimulatory molecule CD28. In contrast to the majority of CD28(pos) cells, granzyme B and perforin were frequently expressed by the CD28(neg) cells, suggesting that they are effector cells. Indeed, these cells were able to kill target cells, in an Ag-specific manner, directly ex vivo. Thus, our findings demonstrate the remarkable long-term persistence in healthy humans of not only influenza-specific memory cells, but also of effector T cells. We further observed that granzyme B expression in influenza-specific CD8 T cells paralleled levels in the total CD8 T cell population, suggestive of Ag-nonspecific bystander activation. Sequencing of TCR alpha- and beta-chains showed that the TCR repertoire specific for this epitope was dominated by one, or a few, T cell clonotype per healthy donor. Moreover, our sequencing analysis revealed, for the first time in humans, that identical clonotypes can coexist as both memory and effector T cells, thereby supporting the principle of multipotent clonotypic differentiation.

• Authors: Cédric Touvrey, Laurent Derré, Estelle Devevre, Patricia Corthesy, Pedro Romero, Nathalie Rufer, Daniel E Speiser
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 182 Issue 11 Pg. 6718-26 (Jun 01 2009) ISSN: 1550-6606 [Electronic] United States
• PMID: 19454666 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CD28 Antigens
• Interleukin-7 Receptor alpha Subunit
• Perforin
• Granzymes

Topics

• CD28 Antigens (analysis)
• CD8-Positive T-Lymphocytes (immunology)
• Cell Differentiation
• Clone Cells (immunology)
• Cytotoxicity, Immunologic
• Granzymes (analysis)
• Humans
• Immunologic Memory
• Immunophenotyping
• Interleukin-7 Receptor alpha Subunit (analysis)
• Perforin (analysis)