Function of alpha beta TCR+ intestinal intraepithelial lymphocytes: Th1- and Th2-type cytokine production by CD4+CD8- and CD4+CD8+ T cells for helper activity.
The immunobiological function of lymphocytes within the epithelium (IELs) of the small intestine is incompletely understood; however, it has been shown that intestinal IEL T cells exhibit cytotoxicity, produce cytokines, and perform some regulatory roles. In this study, we have focused on CD4+, alpha beta TCR+ IELs, which comprise approximately 15-20% of the total population, for helper functions. We have assessed the profile of type 1 or type 2 Th cell cytokines produced in alpha beta TCR bearing CD4+CD8- and CD4+CD8+ (double positive, DP) intestinal IELs by cytokine-specific ELISPOT and by reverse transcription-polymerase chain reaction. Help for B cells taken from Peyer's patches (PP) allowed us to assess IEL function for mucosal antibody responses. Freshly isolated CD4+CD8- IEL T cells contain Th2-type cells, e.g. high numbers of IL-5 secreting (spot forming) cells (SFC) followed by IL-4 and IL-6, while DP T cells have IL-5 and IL-6 producing cells, but not IL-4. In addition to Th2-like cytokine producing T cells, both CD4+ T cell subsets contain IFN-gamma secreting Th1-type cells but neither subset synthesizes IL-2. Stimulation of CD4+CD8- and DP T cells with solid phase mAb anti-CD3 resulted in production of IL-2 in addition to IFN-gamma, IL-5, and IL-6, and this treatment stimulated DP T cells to produce IL-4. When freshly isolated intestinal IEL T cells were separated into CD4+ and CD4- cells, and co-cultured with PP B cells, the former subset supported Ig synthesis including IgA responses, while the later fraction did not.(ABSTRACT TRUNCATED AT 250 WORDS)
Fujihashi
K
K
Department of Oral Biology, University of Alabama at Birmingham 35294.
Yamamoto
M
M
McGhee
J R
JR
Beagley
K W
KW
Kiyono
H
H
D000818:Animals; D000917:Antibody Formation; D016207:Cytokines / Q000096:biosynthesis*; D004797:Enzyme-Linked Immunosorbent Assay; D007413:Intestinal Mucosa / Q000166:cytology*; D008213:Lymphocyte Activation; D051379:Mice; D008809:Mice, Inbred C3H; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D016693:Receptors, Antigen, T-Cell, alpha-beta; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D016207:Cytokines; D012333:RNA, Messenger; D016693:Receptors, Antigen, T-Cell, alpha-beta