Single-cell analyses of CD4+ T cells from alpha beta T cell receptor-transgenic mice: a distinct mucosal cytokine phenotype in the absence of transgene-specific antigen.
Development of distinct CD4+ T cell cytokine phenotypes may be conditioned by the anatomic site in which activation occurs. A double-label in situ hybridization technique was used to characterize co-expression of cytokine mRNA in antigen-specific responses of Peyer's patch (PP), lamina propria (LP), and splenic (SP) CD4+ T cells isolated from alpha beta T cell receptor-transgenic mice. Interleukin (IL)-2 was the dominant cytokine expressed by antigen-stimulated PP and SP populations, though it was expressed by a minority of the activated T cells. Cells that expressed interferon (IFN)-gamma were less frequent, and IL-4, IL-5, and IL-10 were infrequent. In contrast, cells that expressed IFN-gamma or IL-10 were most frequent in the LP population, with lower frequencies of IL-2, and few IL-4- and IL-5-positive cells. Co-expression of two cytokines by the same cell was the exception, regardless of the anatomic site from which the T cells were isolated. The surface phenotype of transgene-positive T cells isolated from each anatomic site was distinct, despite the absence of in vivo exposure to antigen for which the transgenic T cell receptor is specific. These data suggest that the cytokine responses of CD4+ T cells may be conditioned by the microenvironment, independently of specific antigen, and that the LP CD4+ T population has a distinct cytokine expression pattern with counter-regulatory properties that may be important for homeostasis in mucosal immune tissues.
Saparov
A
A
Department of Pathology, University of Alabama at Birmingham 35294, USA.
Elson
C O
CO
Devore-Carter
D
D
Bucy
R P
RP
Weaver
C T
CT
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D002469:Cell Separation; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D000939:Epitopes / Q000096:biosynthesis / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D016130:Immunophenotyping; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D010581:Peyer's Patches / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis / Q000235:genetics*; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D019076:Transgenes / Q000276:immunology*
D016207:Cytokines; D000939:Epitopes; D016693:Receptors, Antigen, T-Cell, alpha-beta