International Immunology, Vol. 5, No. 11, pp. 1473-1481,November 1993
© 1993 Japanese Society for Immunology
Function of 
ß TCR+ intestinal intraepithelial lymphocytes: Th1-and Th2-type cytokine production by CD4+ CD8– and CD4+ CD8+ T cells for helper activity
1 Departments of Oral Biology, Immunobiology Vaccine Center, The University of Alabama at Birmingham, Medical Center Birmingham, AL 35294, USA
2 Departments of Microbiology, Immunobiology Vaccine Center, The University of Alabama at Birmingham, Medical Center Birmingham, AL 35294, USA
3 Departments of Medicine, Immunobiology Vaccine Center, The University of Alabama at Birmingham, Medical Center Birmingham, AL 35294, USA
Correspondence to: Correspondence to: H. Kiyono
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 exhibitcytotoxiclty, produce cytokines, and perform some regulatory roles. In this study, we have focused on CD4+, 
ß TCR+ IELs, which comprise
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 ß 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-
, 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-, 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. Further, purified ß TCR+, CD4+CD8– T cells and DP T cells from IELs when added to PP B cell cultures induced increased numbers of Ig secreting cells. However, CD4–CD8+ T cells which produced a similar profile of cytokines did not provide helper function for B cells. Our study has shown that ß TCR+ T cells from intestinal IELs exhibit Th1- and Th2-type cell functions. Of significant Interest was the finding that DP T cells exhibit cytokine synthesis and helper function in the epithelium of the gastrointestinal tract in addition to CD3+ IELs expressing a classical helper phenotype (CD4+CD8–).
Keywords: ß TCR+ T cells, helper T cells, intraepithelial lymphocytes, mucosal immune response, type 1 and 2 T cells
Received 28 April 1993, accepted 9 July 1993.
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