6 Development and function of γδT cells

Two classes of T cells，namely，T cells expressing T-cell receptor-αβ(TCR-αβ)and T cells expressing TCR-γδ，have been identified in all vertebrates examined to date.It is now clear that mostαβT cells recognize peptide fragments of antigens presented by major histocompatibility complex molecules and are engaged in most characterized cell-mediated antigen-specific immune responses。In contrast，the general rules forγδT-cell recognition remain undefined and the biologic roe ofγδT cells in immune responses is not well understood.We analyzed the cytolytic activity of intraepithelial T cells(IEL)isolated from the small intestines of2-to3-month-old mutant mice rendered deficient in different gene(S)in which the number of IEL expressing either TCR-αβ(αβ-IEL)When compared with wild-type(WT)littermates，cytolytic activity ofγδ-IEL was sharply attenuated in TCR-βmutant(βI D1-/-ii D1)mice but remained unaltered in TCR-αmutant(α…More I D1-/-I D1)mice.The anti-CD3 and anti-TCR-γδmAb-induced IFN-γproduction ofγδ-IEL showed the same TCR-αand TCR-βmutation-dependent variability.In contrast toβI D1-/-I D 1 mice，αI D 1-/-I D 1 mice are predisposed to a marked increase in antibody producing B cells secreting autoantibodies and to germinal center formation.In fact，the traits are comparable to or even exceed those of age-matched wt mice and the cellular mass of lymphoid tissues inαI D1-/-I D1 mice becomes greater than that in control wt mice，either after exposure to environmental antigens or with age.Our present study revealed that，even during2-3 months of young adult age，cytolytic and IFN-γ-producing activities ofγδ-IEL were uniformly high inαI D1-/-I D 1 mice but very low inβI D 1-/-I D 1 mice.Analysis of large intestinalγδ-IEL from2-to3-month-oldαI D 1-/-I D 1 andβI D 1-/-D 1 mice indicated that they were also cytolytic in the former but not in the latter mutant mice，In this context，the persistent colonization of constitutively activated Thy-1 I D 1+E D 1γδ-IEL subset in the intestinal epithelia of youngαI D 1-/sube D 1.Thus，not only theβI D 1 dim i D 1 T cells，but also possibly the activatedγδT cells in the intestinal mucosa，may play an important role in the early stages of development of chronic IBD inαI D 1-/-e D 1 mice。Less：Less

Two classes of T cells, namely, T cells expressing T-cell receptor-αβ(TCR-αβ) and T cells expressing TCR-γδ, have been identified in all vertebrates examined to date. It is now clear that most αβ T cells recognize peptide fragments of antigens presented by major histocompatibility complex molecules and are engaged in most characterized cell-mediated antigen-specific immune responses. In contrast, the general rules forγδT-cell recognition remain undefined and the biologic roe ofγδT cells in immune responses is not well understood.We analyzed the cytolytic activity of intraepithelial T cells (IEL) isolated from the small intestines of 2- to 3-month-old mutant mice rendered deficient in different gene(s) in which the number of IEL expressing either TCR-αβ(αβ-IEL) or TCR-γδ(γδ-IEL) were absent or markedly diminished. When compared with wild-type (WT) littermates, cytolytic activity ofγδ-IEL was sharply attenuated in TCR-β mutant (βィイD1-/-ィエD1) mice but remained unaltered in TCR-α mutant (α … More ィイD1-/-ィエD1) mice. The anti-CD3 and anti-TCR-γδ mAb-induced IFN-γ production of γδ-IEL showed the same TCR-α and TCR-β mutation-dependent variability.In contrast to βィイD1-/-ィエD1 mice, αィイD1-/-ィエD1 mice are predisposed to a marked increase in antibody producing B cells secreting autoantibodies and to germinal center formation. In fact, the traits are comparable to or even exceed those of age-matched wt mice and the cellular mass of lymphoid tissues in αィイD1-/-ィエD1 mice becomes greater than that in control wt mice, either after exposure to environmental antigens or with age. Our present study revealed that, even during 2-3 months of young adult age, cytolytic and IFN-γ-producing activities of γδ-IEL were uniformly high in αィイD1-/-ィエD1 mice but very low in βィイD1-/-ィエD1 mice. Analysis of large intestinal γδ-IEL from 2- to 3-month-old αィイD1-/-ィエD1 and βィイD1-/-ィエD1 mice indicated that they were also cytolytic in the former but not in the latter mutant mice, In this context, the persistent colonization of constitutively activated Thy-1ィイD1+ィエD1 γδ-IEL subset in the intestinal epithelia of young αィイD1-/-ィエD1 mice probably has important implications for the subsequent development of inflammatory bowel disease (IBD) in older αィイD1-/-ィエD1 mice. Thus, not only the βィイD1dimィエD1 T cells, but also possibly the activated γδ T cells in the intestinal mucosa, may play an important role in the early stages of development of chronic IBD in αィイD1-/-ィエD1 mice. Less