Studies on the Pathogenesis of Experimental Autoimmune Renal Tubulointerstitial Disease in Guinea Pigs

Abstract

It has been reported that strain 2 guinea pigs do not develop experimental autoimmune renal tubulointerstitial disease (RTD) by active or passive immunization. Under our experimental conditions strain 2 guinea pigs are susceptible to the induction of RTD. Typical moderate to severe renal lesions were seen 22 days after immunization with rabbit tubular basement membrane in complete Freund’s adjuvant. Most Albany strain guinea pigs had severe RTD. Susceptibility to induction of RTD by passive transfer of antitubular basement membrane autoantibodies was studied in Albany (A) and strain 2 (2) guinea pigs, as well as in A→A, A→2, and 2→A radiation chimeras. Only some Strain 2 guinea pigs had mild to severe renal lesions by day 9, but by day 19 all had typical histologic renal abnormalities. Albany guinea pigs already had moderate to severe RTD by days 9–10. Strain 2 differed from Albany recipients by a noticeable delay in the onset of lesions. Bone marrow transplants between Albany and strain 2 did not affect these susceptibility differences. A→2 recipients responded like strain 2, and 2→A like Albany. This indicates that the delay of onset of RTD in strain 2 is not a defect in the bone marrow-derived inflammatory cells.

Passive transfer of autoimmune disease with isologous IgG1 and IgG2 antibodies to the tubular basement membrane in strain XIII guinea pigs: loss of self-tolerance induced by autoantibodies.

“…Thus, it is not necessary to invoke the direct participation of sensitized cells in the production of renal damage, although helper T cells may be required for autoantibody formation. Our findings may also explain the observation that whole body irradiation can prevent anti-TBM disease, unless the animal is repopulated with normal bone marrow cells (7,8). We suggest that irradiation might act, in part, by depleting the animal of radiosensitive circulating lymphocytes that are essential for autoantibody formation, rather than simply by eliminating nonspecific cells that participate in the inflammatory reaction in the kidney.…”

Murine interstitial nephritis. I. Analysis of disease susceptibility and its relationship of pleiomorphic gene products defining both immune-response genes and a restrictive requirement for cytotoxic T cells at H-2K.

“…In guinea pigs, the passive transfer of aTBM-Ab produces disease only when the recipient has functioning bone marrow (27). Although immune T cells in diseased animals can be renotropic (22), the adoptive transfer of mixed cell populations has not successfully produced disease in guinea pigs (28), possibly because these cells are in a suppressive mode at the time of transfer (E. G. Neilson et al, manuscript in preparation).…”

Inhibitory role of dietary protein restriction on the development and expression of immune-mediated antitubular basement membrane-induced tubulointerstitial nephritis in rats.

“…Highly enriched basement membrane fragments were sonicated, lyophilized, and stored in -700C. Soluble renal tubular antigens (SRTA) were made from these lyophilized membranes using collagenase digestion (14, 16,18 19). Direct immunoflourescence oftubular staining by aTBMAb was qualitatively graded from 0 to 4+ and expressed as mean±SEM for each group ( 16).…”