Selective expansion of Vδ1 + T cells from leprosy skin lesions

Abstract

T cells bearing γδ T-cell receptors (TCRs) are prominent residents of murine epidermis and appear to be important participants in the immune response to infection in human skin. The Mitsuda reaction in leprosy, induced by intradermal challenge with Mycobacterium leprae, provides an opportunity to study the cellular events that mediate a form of delayed-type hypersensitivity (DTH) in skin. T cells bearing γδ TCRs comprise a significant proportion of the T-cell population in these DTH reactions. Presently we have generated T-cell lines from Mitsuda reactions in vitro and compared their TCR repertoire to that found in situ. γδ T cells comprised 20-40% of lines derived from these skin lesions, but < 10% of lines derived from the peripheral blood of the same individuals. Flow-cytometric analysis of variable (V) chain usage in T-cell lines derived from skin lesions indicated that Vδ1 was predominant. Evaluation of the TCR repertoire using PCR indicated that Vδ1-Jδ1 and Vγ2-JγP gene rearrangements were prevalent. In comparison, Vδ2-Jδ1 gene rearrangements predominated in situ. Furthermore, nucleotide sequence analysis of the V-J junction of one T-cell line revealed limited genetic diversity of the γδ TCR. These findings suggest that the Vδ1 subpopulation of γδ T cells in Mitsuda skin reactions selectively outgrows from leprosy skin lesions in vitro. Such Vδ1 + T-cell lines should be useful for determining the relevant antigens and restriction elements in this response to a pathogen in skin. © 1992.