Treatment-resistant Lyme arthritis is associated with immune reactivity to outer surface protein A (OspA) of Borrelia burgdorferi, the agent of Lyme disease, and the major histocompatibility complex class II allele DRB1*0401. The immunodominant epitope of OspA for T helper cells was identified. A homology search revealed a peptide from human leukocyte function-associated antigen-1 (hLFA-1) as a candidate autoantigen. Individuals with treatment-resistant Lyme arthritis, but not other forms of arthritis, generated responses to OspA, hLFA-1, and their highly related peptide epitopes. Identification of the initiating bacterial antigen and a cross-reactive autoantigen may provide a model for development of autoimmune disease.

The patterns of Ag-induced cytokine coexpression in normal, in vivo-primed CD4 memory T cells has remained controversial because the low frequency at which these cells occur has effectively prevented direct ex vivo measurements. We have overcome this limitation by using two-color cytokine enzyme-linked immunospot assays and computer-assisted image analysis. We found CD4 memory cells that simultaneously expressed IL-2, IL-3, IL-4, IL-5, and IFN-γ to be rare (0–10%). This cytokine segregation was seen in adjuvant-induced type 1, type 2, and mixed immunity to OVA, in Leishmania infection regardless of the Ag dose used or how long after immunization the assay was performed. The data suggest that type 1 and type 2 immunity in vivo is not mediated by classic Th1 or Th2 cells but by single-cytokine-producing memory cells.

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Post-transplant monitoring of cellular immunity might be useful in predicting long-term outcomes of kidney transplant recipients. We used an enzyme linked immunoabsorbent spot (ELISPOT) assay to serially measure the frequency of peripheral blood lymphocytes producing interferon-gamma in response to stimulator cells from donors or third parties in 55 primary kidney transplant recipients. Mean frequencies measured during the first 6 months after transplantation correlated significantly with the serum creatinine concentration at both 6 and 12 months following transplantation. The mean frequencies were higher in patients with acute rejection than in those without acute rejection. Multiple regression analyses indicated that the correlations between the early ELISPOT measurements of interferon-gamma and serum creatinine were independent of acute rejection, delayed graft function, or the presence of panel reactive antibodies before transplantation. Patients with low mean frequencies of interferon-producing cells in the early post-transplant period were generally free from acute rejection and exhibited excellent renal function at 6 and 12 months post-transplant. In conclusion, using the ELISPOT assay, we show an independent correlation between early cellular alloreactivity and long-term renal function. Increased levels of early alloreactivity measured with this assay may serve as a surrogate for chronic allograft dysfunction.