Anti‐Interleukin‐2 Receptor Monoclonal Antibody Therapy Supports a Role for Thl‐Like Cells in HgCl₂‐Induced Autoimmunity in Rats

Abstract

Brown-Norway (BN) rats injected with HgCl2 develop an autoimmune disease characterized by a T-dependent polyclonal B-cell activation. Increase in major histocompatibility complex class II molecule expression on B cells concomitant with enhancement of serum IgE concentration supports the involvement of the T helper 2 (Th2)-like subset in the induction of the disease. The mercury disease is autoregulated and does not develop in Lewis (LEW) rats. Considering the reciprocal regulation, well defined in mice, between the Th1 and Th2 subsets, we addressed the role of the Th1-like subset in this disease. Brown-Norway and LEW rats injected with HgCl2 were treated with NDS61, a mouse anti-rat-IL-2R MoAb that blocks mainly Th1 cells. Data reported herein show that: (1) HgCl2 treatment does not modify either the percentage of IL-2R+ cells or IL-2R expression in both BN and LEW rats; (2) treatment of BN rats with NDS61 MoAb does not modify the induction phase of the mercury disease but delays in part the regulation phase; (3) such a treatment leads to some immune abnormalities in LEW rats; (4) HgCl2 markedly potentiates the anti-mouse Ig antibody response in BN rats which probably limits the effect of this treatment. This study supports a role for the Th1-like subset in HgCl2-induced autoimmunity in the rat.

Th1/Th2 cytokine gene expression after mercuric chloride in susceptible and resistant rat strains

“…The cytokine balance, as reflected by the ratio of IL-4 to IFN-y, will be tipped further towards the Th2 compartment after HgC1, in susceptible BN rats. The peak of IFN-y expression in BN occurred at around day 15, when the autoimmune response spontaneously autoregulates [16], supporting the previous suggestion that enhanced Thl function occurs during the regulatory phase [ 12,291. Experiments involving administration of anti-IFN-y antibodies in vivo have also suggested an important regulatory role for this cytokine in HgCktreated BN rats [30].…”

Regulatory CD8+ T Cells Control Neonatal Tolerance to a Th2-Mediated Autoimmunity

“…1). These potential pathogenic responses were followed by a suppressive response that has been shown to involve inhibitory Th1 cells (15,16). In contrast, in animals neonatally exposed to HgCl 2 and rechallenged as adults, these immune dysregulations were either completely abrogated or profoundly attenuated ( Fig.…”

“…Among the numerous autoantibodies produced in SLE and mercury disease, dsDNA represents a major target (14). The HgCl 2 -induced predominant Th2 response is followed by an immunosuppressive reaction with inhibitory Th1-type responses (15,16), while CD8 ϩ T cells are not involved in the initial induction, magnitude, or spontaneous resolution of the mercury disease (17).…”

T Lymphocytes in Mercury-Exposed Workers

“…Morever, we have also found a negative correlation between the levels of IgE and the time of exposure to mercury ( Dantas & Queiroz, 1997-submitted to publication j, thus suggesting that the mechanism of autoregulation described in animals exposed to mercury (7,8,9,19,5) may also occur in man. Despite enhanced humoral immunity, mercury-exposed workers presented reduced numbers of B cells (22; Dantas and Queiroz, 1997-submitted to publication ).…”