Analysis of the inflammatory response in HY-TCR transgenic mice highlights the pathogenic potential of CD4- CD8- T cells.
Transgenic mice expressing a rearranged T cell receptor (TCR)-αβ prematurely at the double-negative stage develop an abnormal population of peripheral T cells that lack CD4 and CD8 expression and are hyper-reactive to anti-TCR antibody stimulation. One such example is the HY-TCR transgenic mice. These mice express a TCR transgenic specific for the HY antigen that is expressed in male but not in female mice. As a result, male mice have an abnormal population of HY(+)/CD4(-)8(-) or HY(+)/CD4(-)CD8(low) T cells that are much lower in female mice. In this study, we investigated the potential patho/physiological function of these cells in vivo using a model of delayed-type hypersensitivity (DTH) reaction: the λ-carrageenan-induced paw edema. Interestingly, while both male and female HY-TCR mice develop a classical biphasic inflammatory response to λ-carrageenan, the degree of inflammation in the former was much higher than that in the latter. This was accompanied by a selective expansion of HY(+)/CD4(-)8(-) and HY(+)/CD4(-)CD8(low) T cells in male mice and by a markedly increased production of typical DTH cytokines compared with cells from female mice. These results were specific since analysis of the inflammatory response of HY-TCR transgenic mice subjected to zymosan-induced peritonitis showed no differences between male and female mice. Together, these findings provide novel evidence for the pathological role of self-reactive CD4(-)CD8(-) T cells, previously described in several autoimmune strains and recently identified in patients suffering from autoimmune diseases such as systemic lupus erythematosus.
Maione
Francesco
F
William Harvey Research Institute, Barts and the London School of Medicine, Charterhouse Square, London, EC1M 6BQ, UK.
Paschalidis
Nikolaos
N
Iqbal
Asif Jilani
AJ
Crompton
Tessa
T
Perretti
Mauro
M
D'Acquisto
Fulvio
F
D000818:Animals; D015551:Autoimmunity / Q000276:immunology*; D002351:Carrageenan / Q000276:immunology*; D016207:Cytokines / Q000032:analysis / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006182:H-Y Antigen / Q000276:immunology*; D006651:Histocytochemistry; D006968:Hypersensitivity, Delayed / Q000276:immunology*; D016130:Immunophenotyping; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D012737:Sex Factors; D013601:T-Lymphocytes / Q000276:immunology*; D015054:Zymosan / Q000494:pharmacology
D016207:Cytokines; D006182:H-Y Antigen; D016693:Receptors, Antigen, T-Cell, alpha-beta; D002351:Carrageenan; D015054:Zymosan