Phenotypic and functional assessment of intraepithelial lymphocytes bearing a 'forbidden' alpha beta TCR.
Differences in the surface antigen phenotype, such as the expression CD8 as an alpha alpha homodimer or the lack of Thy-1, on intestinal intraepithelial lymphocytes (IEL) are related, in part, to alternative differentiation pathways. The relationship of IEL lacking the pan-T cell marker CD5 to these IEL, their TCR repertoire and function has not been examined directly. We explored the TCR repertoire and function of the CD5- IEL subset in relation to the expression of the 'autospecific' V beta 6 TCR in MIs-1a mice and to gamma delta TCR. The results indicate that CD5 expression was absent on the majority of TCR gamma delta IEL (96.9%) and on a significant proportion of TCR alpha beta IEL (25.0%). Virtually all IEL in DBA/2 (MIs-1a) mice that expressed the 'autospecific' V beta 6 TCR were CD5-, and this correlated with the expression of CD8 alpha alpha. To assess the functional capacity of this subset of IEL, we examined proliferation and IL-2 production in response to TCR activation. Although CD5- IEL proliferated in response to anti-CD3, IEL bearing TCR V beta 6, in MIs-1a mice, were not responsive to TCR-mediated activation. Similarly, TCR gamma delta IEL were not responsive to stimulation by anti-TCR gamma delta antibodies. The addition of exogenous IL-2, however, reconstituted the proliferative response of both TCR gamma delta IEL and the TCR V beta 6 expressing IEL. We conclude that the lack of CD5 defines a unique subset of intraepithelial T cells expressing either TCR gamma delta or alpha beta that include potentially autoreactive cells that remain anergic in the absence of IL-2.
Croitoru
K
K
Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
Bienenstock
J
J
Ernst
P B
PB
D000818:Animals; D015703:Antigens, CD / Q000276:immunology*; D018956:CD5 Antigens; D005260:Female; D005434:Flow Cytometry; D007376:Interleukin-2 / Q000096:biosynthesis / Q000502:physiology; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D010581:Peyer's Patches / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology
D015703:Antigens, CD; D018956:CD5 Antigens; D007376:Interleukin-2; D016693:Receptors, Antigen, T-Cell, alpha-beta