REGULATION OF MURINE RESPONSES TO THE KNOWN SEQUENCE POLYMER POLY (L-TYROSINE- L-GLUTAMIC ACID- L-ALANINE-GLYCINE)
Murine immune response to the synthetic sequential polymer (T-G-A-Gly)(,n) is controlled by H-2 linked Ir genes and mapped to the I-A region. The lack of antibody response in nonresponders is not due to defects on B cells, but rather to activation of suppressor cells. Pretreatment of inbred strains of responder mice (A.BY, BALB.B, C57BL/6, C3H.SW/SN) and nonresponder (BALB/c, C3H, SWR) to (T-G-A-Gly)(,n)) with (T-G-A-Gly)(,n) in soluble form either i.p. or i.v. has rendered the mice tolerant to subsequent immunization with either (T-G-A-Gly)(,n) or (T-G-A-Gly)(,n)-MBSA given in complete Freund's adjuvant. The tolerogenic effect of (T-G-A-Gly)(,n) appears to parallel its immunogenicity among the H-2('b) congenic mice i.e. the better the response that can be induced by immunization, the more suppressed is the response by (T-G-A-Gly)(,n) pretreatment. Both cellular (T cell) and humoral (B cell) responses are affected, and the tolerant state appears to last around 21-28 days. The pretreated mice did not show any enhanced or curtailed susceptibility to tolerance induction when they were injected with (T-G-A-Gly)(,n) the second time. Generation of B cell memory in the tolerant mice appears normal, and B cell tolerance was not observed. The tolerance induction is rapid and antigen specific. Adoptive transfer experiments indicate that suppressor cells were responsible for the tolerance in all three strains (BALB/c, A.By, C57BL/6) studied. Studies on responder H-2('b) mice also show the influence of non-H-2 genes in the regulation of suppressor activity; a low-dose-radiation sensitive cell population may be involved. The function of suppressor cells appeared to be associated with the early phase of the immune response because (1) (T-G-A-Gly)(,n)/PBS given after the immunization did not induce tolerance and (2) in vitro cell mixing experiments failed to demonstrate suppressor activities of spleen cells of PETLES from pretreated donors on the immune T cells. In vivo treatment of mice with anti I-J antiserum failed to indicate the presence of I-J determinants carrying suppressor cells for (T-G-A-Gly)(,n).^ Results in this study establish the role of suppressor cells in the regulation of responsiveness, and confirm the observations of Lai et al using antigen binding assays on sera that non-H-2 genes control the magnitude of humoral responses as measured by the PFC responses. In addition, the notion of "H-2 gene control of T cell responsiveness" should be extended to include our findings that non-H-2 genes also play an important role in the regulation of T cell activities. ^
Health Sciences, Immunology
BEELEIN LIN TSAY,
"REGULATION OF MURINE RESPONSES TO THE KNOWN SEQUENCE POLYMER POLY (L-TYROSINE- L-GLUTAMIC ACID- L-ALANINE-GLYCINE)"
(January 1, 1984).
ETD Collection for Thomas Jefferson University.