In 1970, Dixon penned an editorial,“What are sensitized cells doing in glomerulonephritis?”, a skeptical response to a paper showing that glomerulonephritis (GN) patients manifest not only humoral but also cellular responses to glomerular basement membrane (GBM) antigens (1, 2). The view that T cells represent important mediators of GN pathogenesis, rather than, at most, accompanying the supposedly crucial antibody response, proved a hard sell at the time and has remained so for most of the intervening years. Two models of GN are commonly employed. In one, the nephrotoxic nephritis (NTN) model, animals receive heterologous antibody specific for GBM and develop a lesion phenotypically similar to human GN. Many groups have found that both cell-mediated immunity (CMI) and soluble factors contribute to disease in this model. Nevertheless, since NTN is not an autoimmune process and thus almost never occurs in humans, the analogy with human GN pathogenesis is forced and the relevance of CMI remains to be confirmed in other contexts. The second, the experimental autoimmune GN (EAG) model developed by Steblay, in which disease is induced in sheep (3), rats (4), or other animals by active immunization with GBM, may be more suitable in this respect. Antibodies clearly play a role in EAG. For instance, Sado et al. found that GN can be transferred to a naive animal using antibodies purified from EAG rat urine, or even using a defined EAG mAb (5, 6), yielding lesions that are identical to those seen in animals receiving active immunization. Similarly, Kalluri et al. transferred GN in susceptible mice, using serum alone (7), although they noted that this passive transfer procedure caused disease only in wild-type recipients, and not in animals that lacked the T cell receptor. Hence this finding may suggest that T cell activation is a more proximal cause of GN than is antibody deposition per se. Moreover, the observation of antibody-negative GN in some humans (8–10) and in some forms of EAG (11) suggests that CMI alone can produce the disease. After many decades of study, the problem in GN remains to untangle the web of associations between CMI and antibodies. The work of Wu et al. in a recent issue of the JCI (12) now strengthens the case for sensitized T cells as mediators of GN pathogenesis but also raises a number of other critical questions that remain to be addressed. Precedent from other diseases, such as thyroiditis, ovaritis, and allergic encephalomyelitis, shows that CMI can represent the major pathogenic process in autoimmunity, even when circulating antibodies are clearly detectable. However, separating the effects of antibodies and CMI in GN has proved a daunting task. Although T cells are required for anti-GBM antibody production (13), the presence of antibody in the GBM made it difficult to weigh the role of CMI alone. However, in 1984, we described a CMI model of EAG in chickens (14). Naive birds, some of which were bursectomized to prevent humoral responses, were immunized with GBM. Control birds developed GN and their GBM contained IgG, as in human GN patients and mammalian EAG models. Bursectomized animals, as expected, had no detectable antibody on their GBM and developed no antibody response to GBM or other antigens. Nonetheless, these animals manifested normal CMI, and they developed GN of severity equal to or greater than that in controls. Crucially, GN could be induced in naive chickens by transfer of sensitized cells, but not by transfer of antibody (15). Further evidence for T cell immunity in EAG was provided by studies that interfered with T cell function, adherence, or activation (16 …