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PubMed1989

Decrease in phenotypically defined T helper inducer cells (T4+4B4+) and increase in T suppressor effector cells (T8+2H4+) in stable renal allograft recipients.

Two monoclonal antibodies, anti-2H4 and anti-4B4, reciprocally divide the T4+ (CD4+) and T8+ (CD8+) lymphocytes into T4+2H4+, T4+4B4+, T8+2H4+ and T8+4B4+ subsets. The T4+2H4+, T4+4B4+ and T8+2H4+ subsets possess suppressor-inducer, helper-inducer, and suppressor-effector function, respectively, as previously defined in a system of B cell immunoglobulin production. Using monoclonal antibodies, including anti-2H4 and anti-4B4, and flow cytometry, we monitored lymphocyte subpopulations in 66 renal allograft recipients. We found that patients with stable allograft function have a decrease in the percentage of total T4+ lymphocytes from 41.9 +/- 9.5% pretransplant (pre-Tx) to 36.3 +/- 13.9% posttransplant (post-Tx) (P less than 0.05). This decrease was seen mainly in the T4+4B4+ or helper-inducer subset from 20.8 +/- 4.7% (pre-Tx) to 16.0 +/- 6.3% (post-Tx) (P less than 0.005). Patients with stable function were also noted to have an increase in the percentage of total T8+ lymphocytes from 21.3 +/- 10.7% (pre-Tx) to 30.9 +/- 15.4% (post-Tx) (P less than 0.02). Examination of T8 subsets revealed that a statistically significant increase was seen in the T8+2H4+ or suppressor effector subset from 15.5 +/- 9.2% (pre-Tx) to 21.5 +/- 10.2% (post-Tx) (P less than 0.01). Additionally, serial studies on 14 patients revealed an increase in the %T4+2H4+ suppressor-inducer subset from 9.31 +/- 3.64% (pre-Tx) to 15.71 +/- 6.41% (post-Tx) (P less than 0.0025). Since the role of these subsets has not been established in alloimmunity, in vitro allogeneic studies of 2H4-enriched (2H4+) and 2H4-depleted (2H4-) lymphocytes from normal peripheral blood were performed. In the mixed lymphocyte reaction, 2H4+ cells proliferated less than 2H4- cells (cpm ratio 2H4+/2H4-: 0.63-0.84), but 2H4+ cells generated twice as much suppressor activity as 2H4- cells (ratio % suppression 2H4+/2H4-: 1.9-2.3). These results suggest that 2H4+ cells play a role in the suppressor limb of the alloimmune response and that the increase in cells of this phenotype in our transplant population may be responsible for the maintenance of stable allograft function.

Adult↗

PubMed1989

Differential IL-2 receptor expression in renal allograft recipients treated with an anti-IL-2-receptor antibody.

Patients were entered into a randomized trial of prophylaxis for renal allograft rejection by the administration of an anti-human IL-2 receptor antibody, anti-Tac, during the first ten days posttransplant. Interleukin-2 receptor (IL-2 R) expression was measured using two anti-IL-2 R monoclonal antibodies (moAbs), anti-Tac and 1HT4-4H3. These two antibodies recognize closely spaced epitopes on the 55 kD chain of the IL-2 R. IL-2 R expression was examined on peripheral blood small lymphocytes in three groups of patients who received: (A) cyclosporine CsA and prednisone for baseline immunosuppression (n = 9); (B) anti-Tac with CsA and prednisone as baseline immunosuppression (n = 12); and (C) anti-Tac with azathioprine and prednisone as baseline immunosuppression (n = 5). We found that large numbers of T cells express IL-2 receptors despite the presence of anti-Tac (average of IL-2 R-positive cells at day of peak IL-2 R expression 56.0 +/- 20.8% in group A, 65.2 +/- 26.6% in group B, 21.0 +/- 7.4% in group C). IL-2 R expression did not correlate with clinical activity, and the presence or accessibility of epitopes on the same 55 kD chain varied dramatically from patient to patient.

Antibodies, Monoclonal↗