Murine CD8⁺ T suppressors against mycobacterial 65‐kDa antigen compete for IL‐2 and show lack of major histocompatibility complex‐imposed restriction specificity in antigen recognition

Abstract

The mechanism of antigen-specific suppression and reasons for aberrant major histocompatibility complex (MHC) class II restriction mediated by CD8+ T cells was investigated in a previously reported murine model of immunosuppression, generated by intraperitoneal priming with Mycobacterium vaccae. Both the CD4+ T helper cells (Th) and CD8+ T suppressor cell (Ts) of M. vaccae-primed mice recognized the 65-kDa antigen of the bacillus, presented by I-A and I-E, respectively. The CD8+ Ts could inhibit non-antigen-specific proliferation of primed CD4+ T cells induced by the exogenously added interleukin (IL)-2 (concanavalin A-stimulated culture supernatant). For inhibition, the Ts had to be activated by the 65-kDa antigen. The degree of inhibition was dependent upon the amount of added IL-2 and the relative numbers of primed CD8+ and CD4+ T cells. On incubation with antigen-presenting cells, and the 65-kDa antigen, the primed CD8+ T cells absorbed IL-2 as efficiently as primed CD4+ T cells. Based on this, it was concluded that the primed CD8+ T cells induced suppression by competition for IL-2. Employing the same model, the MHC restriction of recognition of the suppressor epitope of the 65-kDa antigen by the CD8+ Ts was investigated. The epitopes presented by diverse MHC class II molecules, such as self I-A, I-E and even allogeneic I-E were similar, because they were recognized by the same population of primed CD8+ Ts. Further, immunization of C57BL/6 mice with Ltk-cells expressing H-2 DkKk alloantigens, stimulated CD8+ T cells capable of recognizing M.vaccae 65-kDa antigen. Based on these data, it was proposed that recognition of the suppressor epitope of the 65-kDa antigen by the primed CD8+ Ts exhibits lack of restriction specificity imposed by MHC diversity.

Interactions between T Cells Responding to Concurrent Mycobacterial and Influenza Infections

“…However, this competition is greater between T cells specific for the same peptide-MHC complex than for T cells specific for different peptide-MHC complexes (47), and 3A9 and 5CC7 T cells are restricted by different class II Ags. Some have also suggested that T cells may compete for cytokines such as IL-2 (48). Recent work has also demonstrated that recently activated T cells can inhibit the activation of naive T cells in vitro (49).…”

Antigen-presenting cells (APC) of mice with chronic graft-versus-host disease (GVHD) cause excessive activation-induced death of T helper cells

“…The sonicates of M. vaccae and S. enteritidis and the immunodominant 65-kD antigen of the former were prepared as described earlier [12].…”

“…The antibodies were raised by repeated immunizations with 65-kD antigen of M. vaccae (purified as described earlier [12]), in FIA at 10-day intervals. Rabbit immunization was repeated until a precipitin titre (by agar gel diffusion) of 1:16 was reached.…”

Immunomodulatory properties of porins of some members of the family Enterobacteriaceae

“…The supernatants were filtered through 0.22m-pore-size membrane filter (Millipore), and their protein content was assayed. The 65-kDa antigen was purified from the sonicate of M. vaccae by preparative agarose isoelectrofocusing, using ampholines (pH range of 3.5 to 5.0) as described earlier (22).…”