Cellular events in protein tolerant inbred rats. I. The fate of thoracic duct lymphocytes and memory cells during tolerance induction to human serum albumin
✍ Scribed by E. B. Bell; F. L. Shand
- Publisher
- John Wiley and Sons
- Year
- 1973
- Tongue
- English
- Weight
- 909 KB
- Volume
- 3
- Category
- Article
- ISSN
- 0014-2980
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✦ Synopsis
Abstract
(AS2 x AS)F~1~ hybrid rats were made completely or partially tolerant to an adjuvant challenge of human serum albumin (HSA) by prior treatment with fluid HSA (tolerogen). Single doses (10 μg to 200 mg) of fluid HSA failed to elicit a detectable immune response. However, rats made partially tolerant by repeated small doses (10 – 100 μg) synthesized significant quantities of antibody in response to the treatment.
Completely unresponsive rats (100 mg fluid HSA 3 x/week for 8 weeks) contained no detectable antigen‐binding antibody in their serum and no plaque‐forming cells (PFC) in their spleens. Thoracic duct lymphocytes from these animals failed to respond when adoptively transferred to irradiated, bone marrow restored recipients and did not inhibit the response of equal numbers of normal thoracic duct cells. Normal lymphocytes responded normally in completely tolerant rats, whether the recipients were irradiated or not. Cells from the bone marrow of tolerant rats were able to restore HSA responsiveness to irradiated rats within weeks of repopulation.
Partial tolerance was characterized by a reduction in PFC per spleen, a diminished antigen‐binding capacity (ABC) in the serum, a rapid decline in ABC with time and inhibition or abolition of a memory response. Analysis of the dosage requirements for HSA‐tolerance failed to support the concept that tolerance was induced at two separate dosage thresholds of antigen, i.e. “high” and “low” zone tolerance. To the contrary, the degree of unresponsiveness increased continuously in proportion to the dose of antigen and the number of injections, implying that tolerance induction can be explained by a single mechanism at all doses.