Role of the CD5 molecule on TCR {gamma}{delta} T cell-mediated immune functions: development of germinal centers and chronic intestinal inflammation

doi:10.1093/intimm/dxg006

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International Immunology, Vol. 15, No. 1, pp. 97-108, January 2003
© 2003 Japanese Society for Immunology

Role of the CD5 molecule on TCR ${gamma}$ ${delta}$ T cell-mediated immune functions: development of germinal centers and chronic intestinal inflammation

Atsushi Mizoguchi¹^,2^,4, Emiko Mizoguchi¹^,2^,4, Ype P. de Jong²^,3^,5, Hiroko Takedatsu¹^,4, Frederic I. Preffer¹^,4, Cox Terhorst²^,3^,5 and Atul K. Bhan¹^,2^,4

¹ Department of Pathology and ² Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital, Boston, MA 02114, USA ³ Division of Immunology, Beth Israel Deaconess Medical Center, Boston, MA 02115, USADepartments of ⁴ Pathology and ⁵ Immunology, Harvard Medical School, Boston, MA 02115, USA

Correspondence to: A. Mizoguchi, Immunopathology Unit, Warren 501, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA. E-mail: amizoguchi{at}partners.org
Transmitting editor: R. S. Geha

Although CD4⁺ T cells form a major subset of TCR ${alpha}$ ßT cells, only a small number of TCR ${gamma}$ ${delta}$ T cells express CD4. Factorscontributing to the down-regulation of CD4⁺ TCR ${gamma}$ ${delta}$ T cells havenot been identified. The CD5 molecule is expressed on most TCR ${gamma}$ ${delta}$ T cells in the spleen, whereas only a few intestinal intraepithelialTCR ${gamma}$ ${delta}$ T cells express this molecule in wild-type mice and TCRßmutant (ß^–/–) mice. Unexpectedly, in thepresent studies, the lack of CD5 led to a remarkable increaseof a CD4⁺ TCR ${gamma}$ ${delta}$ T cell subset in CD5^–/–ß^–/–mice. The CD4⁺ TCR ${gamma}$ ${delta}$ T cells were also detectable in MHC II^–/–CD5^–/–ß^–/–triple-mutant mice. This CD4⁺ TCR ${gamma}$ ${delta}$ T cell subset provided helpin Mycobacterium-induced germinal center (GC) formation andshowed a T_h-like cytokine profile. In contrast, CD5⁺ TCR ${gamma}$ ${delta}$ T cellssuppressed the CD4⁺ TCR ${gamma}$ ${delta}$ T cell-mediated GC formation, presumablyby eliminating this CD4⁺ subset. Unlike intraepithelial ${gamma}$ ${delta}$ T cells,>30% of TCR ${gamma}$ ${delta}$ T cells in the colonic lamina propria (LP) expressedCD5. The lack of CD5 also led to increased numbers of CD4⁺ TCR ${gamma}$ ${delta}$ T cells in the colonic LP and increased susceptibility to developmentof chronic colitis in ß^–/– mice. Celltransfer studies suggest that CD5⁺ TCR ${gamma}$ ${delta}$ T cells are capable ofselectively eliminating CD4⁺ TCR ${gamma}$ ${delta}$ T cells in the intestine. TheCD4⁺ TCR ${gamma}$ ${delta}$ T cells possess immune functions similar to CD4⁺ TCR ${alpha}$ ßT cells.

Keywords: CD4, immune deficiency, inflammatory bowel disease, regulatory, TCR ß knockout mice

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[Abstract] [Full Text] [PDF]

International Immunology

Role of the CD5 molecule on TCR T cell-mediated immune functions: development of germinal centers and chronic intestinal inflammation

Role of the CD5 molecule on TCR ${gamma}$ ${delta}$ T cell-mediated immune functions: development of germinal centers and chronic intestinal inflammation