02536nas a2200433 4500000000100000008004100001260001300042653001000055653000900065653003100074653004000105653001400145653001100159653002000170653002300190653001100213653002500224653001800249653000900267653001600276653003000292653004300322653002700365653002700392100001300419700001400432700001400446700001400460700001400474700001500488700001600503700001100519700001200530245014300542300001100685490000800696520138400704022001402088 2002 d c2002 Jun10aAdult10aAged10aCD4-Positive T-Lymphocytes10aComplementarity Determining Regions10aCytokines10aFemale10aGene Expression10aGranuloma Annulare10aHumans10aImmunohistochemistry10aInterleukin-210aMale10aMiddle Aged10apolymerase chain reaction10aReceptors, Antigen, T-Cell, alpha-beta10aSequence Analysis, DNA10aTranscription, Genetic1 aMempel M1 aMusette P1 aFlageul B1 aSchnopp C1 aRemling R1 aGachelin G1 aKourilsky P1 aRing J1 aAbeck D00aT-cell receptor repertoire and cytokine pattern in granuloma annulare: defining a particular type of cutaneous granulomatous inflammation. a957-660 v1183 a

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.

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