Autologous mixed lymphocyte reactions in NZB mice: analysis in recombinant inbred lines shows a T cell defect unrelated to autoantibody production

Abstract

The autologous mixed lymphocyte reaction (AMLR) has been examined in the AMLR-deficient strain, NZB, in C58 mice, which have normal AMLR responses, and in the (NZB x C58) recombinant inbred (NX8 RI) lines. Half of the NX8 RI lines had deficient AMLR and half were comparable in reactivity to the C58 parent strain. AMLR unresponsiveness did not correlate in the NX8 RI lines with H-2 or any other marker known to affect immune recognition. Non-T cells from H-2k NX8 RI lines which had deficient AMLR were able to stimulate an MLR when cultured with T cells of C58 origin. AMLR-positive H-2d lines responded to NZB stimulators, whereas NZB T cells did not respond to any of the H-2d NX8 RI lines but did exhibit strong alloreactivity. Thus, the AMLR defect in NZB mice is due to a T cell lesion. Furthermore, since AMLR deficiency in the NX8 RI lines did not correlate with a positive Coombs test or the production of naturally occurring thymocytotoxic antibody, we conclude that autoimmunity in NZB mice is a complex disease resulting from the inheritance of multiple independently segregating genes.

A recombination event in the 5′ flanking region of the Ly-6C gene correlates with impaired expression in the NOD, NZB and ST strains of mice.

“…These two strains of mice also exhibit a depressed syngeneic mixed lymphocyte reaction (SMLR), which, as a measure of the proliferative response of T cells to accessory cells bearing self-MHC class II determinants, represents an immunoregulatory cellular interaction (Smith and Pasternak, 1978;Glimscher et al, 1981;Serreze and Leiter, 1988). Analysis of recombinant inbred lines derived from NZB indicates cosegregation of the defect in Ly-6C expression and decreased responsiveness in the SMLR (Bocchieri et al, 1981). Initial Southern blots of genomic DNA from NOD, NZB and ST with a cross-hybridizing Ly-6 cDNA probe revealed a multiple banding pattern consistent with the Ly-6.…”

Age-Related Decline in Cell-Mediated Immunity in the C58 Leukemic Mouse Strain

“…MLR and AMLR cultures were performed, as pre viously reported [Bocchieri et al, 1981], in triplicate in 96-well microtiter plates (Falcon No. 3072), con taining 8 X 10s nylon wool nonadherent T cells and 3 X 10s mitomycin C-treated whole spleen cells, and cultured for 4 and 5 days, respectively, in a 5% CCh/humidified-air incubator.…”

“…Our previous studies of the immune reactions of young adult ani mals of this strain described normal cellmediated immune functions [Bocchieri et al, 1981;Bocchieri et al, 1985]. The only aberrant finding was the presence of antithy mocyte autoantibody in approximately half of the females tested at 6 months of age and older [Bocchieri et al, 1982], Earlier reports in the literature on cellmediated immune responses in the AKR, HRS hr/+, and HRS hr/hr retroviral-induced leukemic mouse strains found deficits only after the occurrence of disease that were associated with the presence of suppressor cell activity [Senders et al, 1983;Morrissey et al, 1980;Metcalf and Moulds, 1967;Colavo et al, 1975;Martig and Tribble, 1974;Roman and Golub, 1976;Russell and Go lub, 1978;Mulder et al, 1978;Norman et al, 1981], Our present studies have extended our earlier work on cell-mediated immunity to older mice of the C58 strain, investigating possible immunologic contributions to the development of their leukemia.…”

Impaired mobility of human t lymphocyte surface molecules during inactive systemic lupus erythematosus. relationship to a defective camp pathway

“…Indeed, diverse T cell dysfunctions appear to exist independently of the interaction of autoantibody with T lymphocytes (17,18).…”

“…However, anti-T cell autoantibodies do not appear to induce primary cellular dysfunctions in T lymphocytes (16). Indeed, diverse T cell dysfunctions appear to exist independently of the interaction of autoantibody with T lymphocytes (17,18).…”