Cellular induction of chronic allotype suppression of IgG2a in Ighb/b homozygous mice and its abrogation by in vivo treatment with anti-CD8 monoclonal antibody.

Abstract

We report here the successful induction of allotype suppression in homozygous Ighb/b mice (CB20 or C57BL/6) by neonatal injection of T splenocytes from Igha congenic sensitized mice (BALB/c or BC8, respectively). The sensitization of the T cell donors was achieved by two intravenous injections of B splenocytes from Ighb congenic mice. Treated homozygous Ighb/b mice developed, as of 16-24 wk of age, a chronic suppression of Igh-1b expression (IgG2a of Ighb haplotype). The other productions tested (IgM, IgD, and IgA) of Ighb haplotype were unaffected. In vivo treatment with cytotoxic anti-CD4 or anti-CD8 mAb of mice subjected to chronic Igh-1b suppression clearly showed that CD8+ lymphocytes (suppressor or cytotoxic cell) were essential for the maintenance of the suppression. The suppression was indeed abrogated after a 1-wk treatment with anti-CD8 mAb containing culture supernatant, whereas, the anti-CD4-treated mice continued to be subjected to suppression. This anti-CD8 in vivo treatment was shown to have no effect on thymus but to severely reduce the percentages of CD8+ cells in spleen and in peripheral blood without affecting the percentages of CD4+ cells, leading to a large and rapid Igh-1b expression (up to 0.5 mg per ml of serum, the day after the end of the treatment). This suppression abrogation, and thus the Igh-1b expression, was either transient or permanent. When it was transient, a second 1-wk treatment with anti-CD8 mAb containing culture supernatant induced once again a rapid and significant production of Igh-1b (up to 0.3 mg of Igh-1b per ml of serum).

Requirement for CD8+ T cells in the development of airway hyperresponsiveness in a marine model of airway sensitization.

“…In the present study, we have investigated this issue by analyzing the consequences of in vivo CD8 T-cell depletion before sensitization on IgE production, development of immediate cutaneous reactivity and AHR in a mouse model of airway sensitization. In contrast to other approaches (44)(45)(46), we chose the combination of thymectomy and injection of monoclonal anti-CD8 antibody to deplete CD8 + T cells. Analysis of the peripheral lymphoid tissues showed a virtually complete depletion of the CD8 + T cell 9opulation after this treatment.…”

Depletion of OX-8 lymphocytes from the blood and airways using monoclonal antibodies enhances the late airway response in rats.

“…The OX-8+ phenotype is expressed on rat cytotoxic T cells and noncytotoxic T suppressor cells (Ts) (24), as well as on a subset of natural killer cells (25) nal antibodies have demonstrated a suppressive role for CD8' cells (31,32). In BB/Wor rats, a model of spontaneous diabetes mellitus, OX-8 depletion prevented lymphocytic destruction of pancreatic beta cells (33).…”

Central tolerance induction in natural immunoglobulin-allotype-specific T cells

“…The suppression-induction phase in T cell recipients requires cooperation between CD4 + and CD8 + T cells, both specific for IgG 2a b [14,15]. The suppression effectors are MHC class I-restricted, cytotoxic CD8 + T cells [16,17], which use, alternatively or concomitantly, perforin-and Fas-mediated pathways to continuously eliminate B cells committed to IgG 2a b production [18].…”