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Phenotypic and functional characterization of CD4 T cells expressing killer Ig-like receptors
Jeroen van Bergen1, Allan Thompson, Arno van der Slik
1Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands. J.van_Bergen@lumc.nl
Insights
Killer Ig-like receptors (KIR) are present on CD4 T cells in most individuals, increasing with age. These cells are primarily effector memory Th1 cells, distinct from typical CD4 T cells.
Area of Science:
- Immunology
- Cell Biology
Background:
- Killer Ig-like receptors (KIR) are typically found on NK cells, gammadelta T cells, and CD8 T cells.
- The presence and characteristics of KIR-expressing CD4 T cells in healthy individuals remain controversial.
Purpose of the Study:
- To definitively establish the prevalence of KIR-expressing CD4 T cells in healthy individuals.
- To characterize their frequency, surface phenotype, cytokine profile, and antigen specificity.
Main Methods:
- Flow cytometry analysis of peripheral blood mononuclear cells.
- T-cell receptor (TCR) triggering and cytokine production assays (IFN-gamma, IL-4, IL-10, IL-17).
- Antigen specificity assessment using HLA class II-restricted recall antigens.
Main Results:
- KIR-expressing CD4 T cells are present in most individuals and increase with age.
- These cells predominantly exhibit an effector memory phenotype (CD57+, CD28-, CCR4-, CCR7-).
- KIR(+) CD4 T cells produce primarily IFN-gamma and respond to recall antigens in an HLA class II-restricted manner.
Conclusions:
- KIR-expressing CD4 T cells represent a significant, previously unrecognized subset of effector memory Th1 cells.
- These cells are primarily HLA class II-restricted and contribute to cellular immunity.
Abstract:
Killer Ig-like receptors (KIR) are commonly found on human NK cells, gammadelta T cells, and CD8 T cells. Although KIR(+) CD4 T cells are found in certain patients, their prevalence in healthy donors is controversial. We now provide definitive proof that such cells are present in most individuals, and report on their frequency, surface phenotype, cytokine profile, and Ag specificity. The number of KIR(+) CD4 T cells detected in peripheral blood increased with age. In contrast with regular KIR(-) CD4 T cells, the majority of KIR(+) CD4 T cells lacked surface expression of CD27, CD28, CCR4, and CCR7, but did express CD57 and 2B4. In addition, KIR were detected on approximately one-tenth of CD28(-) and CD57(+) memory CD4 T cells. In line with the absence of the Th2 marker CCR4, the KIR(+) CD4 cells produced mainly IFN-gamma and little IL-4, IL-10, or IL-17 upon TCR triggering. Furthermore, the KIR(+) population contained cells that responded to recall Ags in an HLA class II-restricted fashion. Together, our data indicate that KIR-expressing CD4 T cells are predominantly HLA class II-restricted effector memory Th1 cells, and that a significant, previously unrecognized fraction of effector memory Th1 cells expresses KIR.
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