Interleukin 2 abrogates the nonresponsive state of T cells expressing a forbidden T cell receptor repertoire and induces autoimmune disease in neonatally thymectomized mice

José L. Andreu-Sánchez, Ignacio Moreno De Alborán, Miguel A.R. Marcos, Arsenio Sánchez-Movilla, Carlos Martínez-A, Guido Kroemer

Research output: Contribution to journalArticlepeer-review

83 Citations (Scopus)

Abstract

Under physiological conditions, the vast majority of T cells differentiate in the thymus, an organ that provides an optimal microenvironment for T cell maturation and shapes the T cell repertoire via positive and negative selection processes. In the present report, we demonstrate that neonatal thymectomy of CBA/H mice results in a diminution of T cells in peripheral lymphoid organs (spleen, lymph nodes), but is followed by a marked transient (12 wk) increase in Thy-1+ CD3+ cells in the peritoneal cavity. These cells exhibit predominantly a double-negative (CD4-CD8-) phenotype among which products of the T cell receptor (TCR) Vβ11 gene family (i.e., an I-E-reactive TCR normally deleted in I-E-bearing CBA/H mice) are selectively overexpressed. This observation suggests that, under athymic conditions, T cell differentiation and/or accumulation may occur in the peritoneal cavity. Intraperitoneal inoculation of an interleukin 2 (IL-2) vaccinia virus construct that releases high titers of human IL-2 in vivo induces conversion of these double-negative T cells to either CD4+CD8- or CD4-CD8+ single positives, and allows in vitro stimulation of TCR Vβ11-bearing cells with a clonotypic anti-Vβ antibody. Since IL-2 induces autoimmune manifestations (DNA autoantibodies, rheumatoid factors, and interstitial nephritis) in thymectomized CBA/H mice, but not in sham-treated littermates, this lymphokine is likely to enhance the autoaggressive function of T cells that bear forbidden, potentially autoreactive TCR gene products and that are normally deleted in the thymus.

Original languageEnglish
Pages (from-to)1323-1329
Number of pages7
JournalJournal of Experimental Medicine
Volume173
Issue number6
Publication statusPublished - 1 Jun 1991
Externally publishedYes

Cite this