LACK OF ENHANCED T-HELPER CELL-FUNCTION IN UREMIC PATIENTS WITH CIRCULATING ALLOREACTIVE ANTIBODIES

Some uremic patients with a history of blood transfusion, pregnancy, a nd previous transplantation maintain high levels of alloreactive cytot oxic antibodies in the absence of continuous exogenous allogenic stimu li and are thus considered sensitized to the major histocompatibility proteins. To differentiate into antibody-producing cells, B lymphocyte s must interact with T-helper (CD4(+)) cells, Whether ongoing help fro m these cells is necessary for the B cells to continue producing cytot oxic alloreactive antibodies in these sensitized uremic patients is un known. To gain insight into the cellular mechanisms that are associate d with sustained alloantibody production, T cell activation markers we re measured and specific and nonspecific T-helper cell function was st udied in three uremic groups with different levels of panel reactive a ntibodies: 10 patients whose sera reacted to more than 80% of a panel of normal lymphocytes for at least 6 months before the study were high ly sensitized, 20 patients whose sera reacted to less than 80% of the panel were moderately sensitized and 10 nonsensitized patients whose s era did not react to any cell on the panel. The number of total and ac tivated T-helper cells was similar in the highly sensitized and nonsen sitized patients. Peripheral blood lymphocyte proliferation in respons e to plant lectins, soluble OKT3, or alloantigens was similar in the t hree uremic groups. The spontaneous proliferation of pure T-helper cel ls and proliferative responses to immobilized OKT3 or alloantigens wer e also similar in highly sensitized and nonsensitized patients, Allore active interleukin-B-producing cell frequencies with pure CD4(+) cell as responding cells were 771 +/- 77.9/10(6) cells in highly sensitized , 945 +/- 252/10(6) cells in nonsensitized, and 973 +/- 114/10(6) cell s in controls (P = not significant). Panel reactive antibody levels di d not correlate with any of the measures of T helper responses. There was a significant decrease of peripheral blood lymphocyte responses to alloantigens and anti-CD3 antibody in all uremic patients as compared with normals, suggesting a dysfunction in accessory cells that was qu antitatively similar in sensitized and nonsensitized patients. in spit e of the continuous production of alloantibodies by B cells, there is no evidence of either specific or nonspecific enhancement of T-helper cell function in sensitized patients. The absence of T cell immunity t o alloantigens suggests that sustained activation of T-helper cells wi th subsequent interleukin-2 production is not necessary to maintain al loreactive B cell function.