Murine interstitial nephritis. VIII. Characterization of Igh-V restriction determinants in the development of anti-idiotypic immunity using blocking antibodies

Inhibition of murine nephritogenic effector T cells by a clone-specific suppressor factor.

“…Although we were initially impressed that exposure to TsF2 induced an indefinite state of unresponsiveness, this finding is consistent with the complete inhibition of nephritogenic T cell expression and disease activity documented in previous studies (18)(19)(20). The fact that the cell line and clones continued to grow well immediately after exposure to TsF2 and when repassaged, led us to examine whether we could identify some alteration in cell-surface receptors or cytokine expression which might explain their inability to function.…”

“…P1, a synthetic peptide derived from the cDNA sequence of 3M-1 (LLRRRHGDRRSTMSAEVP) was manually synthesized by the simultaneous multiple peptide method of Houghten (29,30 T cell lines (M52 and M61) and clones. CD8+ T cell lines and clones were isolated from immunized mice as previously described (26) and propagated by weekly passage with 20 jig/ml antigen (SRTA, P1, or PPD), 20% MLA-144 supernatants as a source or IL-2 and other growth factors (31) (19,20). Induced splenocytes were then depleted with aCD4 Ab (from GK 1.5 hybridoma [33] ) and a mixture of guinea pig and rabbit C. Freezethaw lysates were made of the remaining CD8+ T cells.…”

“…The other subset is DTH reactive but effects less efficient cytotoxicity to 3M-i-expressing tubular epithelial cells (26). Since previous studies suggest that these clones should be the direct target of TsF2 (18, 19), we were in a unique position to characterize the state of clonal inactivation resulting from coculture with a suppressor factor. Our studies show that co-culture with TsF2 results in functional inactivation of nephritogenic M52 cells.…”

“…The CD4+ suppressor T cells (Tsl ) inhibit an early stage in the differentiation of the nephritogenic CD8 + effector T cells which mediate aTBM disease, and also induce a population of CD8 + suppressor T cells (18)(19)(20). These CD8+ Ts cells (Ts2), or soluble proteins secreted by Ts2 cells (TsF2), directly inhibit the function of bulk populations of tubular antigen-specific CD8+ effector cells through a noncytotoxic mechanism ( 18,19). While the molecular definition of suppressor factors is still controver-sial, increasing evidence supports their being closely related to conventional TCR chains (21)(22)(23)(24).…”