Elimination of CD8+ thymocytes in transgenic mice expressing an anti-Lyt2.2 immunoglobulin heavy chain gene

Abstract

Individual T cell populations are characterized by specific surface proteins, namely by the T cell receptor complex (TCR) and by two accessory molecules, CD8 (Lyt2) and CD4 (L3T4). CD8 and CD4 are required for T cell interactions with class I or class II major histocompatibility complex molecules. In the thymus, immature CD8-4- TCR- cells differentiate, possibly via a short stage of CD8+4- thymocytes, into CD8+4+ TCR+ T cells and mature further into the main T cell populations, the CD8+4- TCR+ cytotoxic T lymphocytes and the CD4+8- TCR+ T helper cells. In order to analyse the differentiation steps involving CD8, we generated transgenic mice expressing μ heavy chain genes from an anti-Lyt2.2 hybridoma. Transgenic lines expressing either the complete (μ(sm)) or only the secreted μ protein (μ(s)) suffer from a severe depletion of their CD8+4+ thymocytes affecting also the mature CD8+4- and CD4+8- populations. The depletion is correlated to the expression of transgenic μ-chain proteins within thymocytes. This intrathymocyte expression of the μ chain prevents CD8-4- thymocytes from further differentiation, most probably via intracellular interactions between μ heavy chain and CD8 proteins. These results show that CD8 plays an important role during thymocyte maturation.