Human Th1 cells that express CD300a are polyfunctional and after stimulation up-regulate the T-box transcription factor eomesodermin.
Human naïve CD4 T cells express low levels of the immunomodulatory receptor CD300a, whereas effector/memory CD4 cells can be either CD300a(+) or CD300a(-). This suggested that CD300a expression could define a specific subset within the effector/memory CD4 T cell subpopulations. In fact, ex vivo analysis of the IFN-gamma producing CD4 T cells showed that they are enriched in the CD300a(+) subset. Moreover, stimulated CD4 T cells producing TNF-alpha and IL-2 besides IFN-gamma (polyfunctional) are predominantly CD300a(+). In addition to producing markedly higher levels of Th1-associated cytokines, the stimulated CD300a(+) CD4 T cells are distinguished by a striking up-regulation of the T-box transcription factor eomesodermin (Eomes), whereas T-bet is up-regulated in both CD300a(+) and CD300a(-) activated CD4 T cells to similar levels. The pleiotropic cytokine TGF-beta1 has a determinant role in dictating the development of this Th1 subset, as its presence inhibits the expression of CD300a and down-regulates the expression of Eomes and IFN-gamma. We conclude that CD300a(+) human Th1 cells tend to be polyfunctional and after stimulation up-regulate Eomes.
Narayanan
Sriram
S
Receptor Cell Biology Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, United States of America.
Silva
Rodolfo
R
Peruzzi
Giovanna
G
Alvarez
Yelina
Y
Simhadri
Venkateswara R
VR
Debell
Karen
K
Coligan
John E
JE
Borrego
Francisco
F
D015703:Antigens, CD / Q000378:metabolism*; D002465:Cell Movement / Q000187:drug effects; D016764:Cell Polarity / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D007156:Immunologic Memory / Q000187:drug effects; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D016131:Lymphocyte Subsets / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010641:Phenotype; D011971:Receptors, Immunologic / Q000378:metabolism*; D020825:T-Box Domain Proteins / Q000235:genetics*; D018417:Th1 Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics*
D015703:Antigens, CD; C515070:CD300A protein, human; C491199:EOMES protein, human; D011971:Receptors, Immunologic; D020825:T-Box Domain Proteins; D053773:Transforming Growth Factor beta1; D007371:Interferon-gamma