T-cell receptor repertoire and cytokine pattern in granuloma annulare: defining a particular type of cutaneous granulomatous inflammation.
Granuloma annulare is a common granulomatous infiltration of the skin of unknown etiopathogenesis. We analyzed granuloma annulare biopsies in 11 patients and could find in all patients significant numbers of CD4-T cells. These cells showed a broad usage of the different T cell receptor Vbeta families and a rather unbiased repertoire when the complementary determining region 3 spectra were analyzed by the Immunoscope technique. Comparison with the peripheral blood mononuclear cell repertoire, however, identified in all patients few skin-specific expansions, which were for one patient also present in two distinct skin sites. Extensive sequence analysis of the complementary determining region 3 region confirmed the presence of a limited number of skin-specific expansions together with various nonspecific T cell infiltrations. Analysis of the intralesional cytokine expression revealed abundant production of interleukin-2, which was not dominant in granulomas from leprosy patients and was not reflected by the cytokine profile in peripheral blood mononuclear cells. These results demonstrate the capacity of the granulomatous response to recruit T cells in high numbers with only few clones expanding specifically. The high local production of interleukin-2 might thereby play an important role in the nonspecific attraction of T cells to the granulomatous site.
Mempel
Martin
M
Institut Pasteur, Unité de Biologie Moléculaire du Gène, INSERM U277, Department of Immunology, Paris, France. m.mempel@lrz.tum.de
Musette
Philippe
P
Flageul
Beatrice
B
Schnopp
Christina
C
Remling
Roland
R
Gachelin
Gabriel
G
Kourilsky
Philippe
P
Ring
Johannes
J
Abeck
Dietrich
D
D000328:Adult; D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry / Q000166:cytology / Q000276:immunology*; D022801:Complementarity Determining Regions / Q000235:genetics / Q000276:immunology; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D005260:Female; D015870:Gene Expression / Q000276:immunology; D016460:Granuloma Annulare / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry; D007376:Interleukin-2 / Q000235:genetics / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis / Q000235:genetics / Q000276:immunology; D017422:Sequence Analysis, DNA; D014158:Transcription, Genetic / Q000276:immunology
D022801:Complementarity Determining Regions; D016207:Cytokines; D007376:Interleukin-2; D016693:Receptors, Antigen, T-Cell, alpha-beta