CD4-1 AND CD8+ TYPE-2 T-CELL SUBSETS IN HUMAN LEISHMANIASIS HAVE DISTINCT T-CELL RECEPTOR REPERTOIRES( TYPE)

The mechanism of protective immunity and immunologic resistance agains t intracellular pathogens is believed to involve the activation of Ag- specific T cells. The T cells involved in protection/resistance to Lei shmania can be studied using localized American cutaneous leishmaniasi s (LCL) as a model, because the disease is often self-healing. Our stu dy was undertaken to identify specific T cell populations that had acc umulated in LCL lesions on the basis of TCR Vbeta gene usage. RNA was derived from skin lesions and blood of eight LCL patients, as well as from purified CD4+ and CD8+ subsets from the lesions and blood of thre e patients. After synthesis of cDNA, Vbeta gene usage was assessed by polymerase chain reaction. In all eight patients, several Vbeta gene f amilies were overrepresented in lesions compared to blood. More import antly, the TCR Vbeta repertoires of both lesional CD4+ and CD8+ subset s were skewed compared to the repertoire of the respective subsets in the blood of the same donor. The overrepresented Vbetas in the CD4+ an d CD8+ subsets from lesions were in most instances disparate, particul arly with the Vbeta6 TCR skewed in the lesional CD8+ subset. Not only were the TCR repertoires of the overrepresented Vbeta in the lesional CD4+ and CD8+ subsets generally distinct, but the cytokine mRNA expres sed by these subsets were also discrete. Strikingly, the CD4+ subset w as characterized by IFN-gamma mRNA expression and the CD8+ subset by I L-4 and IL-10 mRNA expression. These data indicate that the pathogenes is of human leishmaniasis may be explained by the balance of CD4+ type 1 and CD8+ type 2 T cells, which probably recognize distinct sets of Ag.