TY - JOUR
T1 - Selective reversal of H‐2‐linked genetic unresponsiveness to lysozymes
T2 - II. Alteration in the T helper/T suppressor balance, owing to gene(s) linked to Ir‐2, leads to responsiveness in BALB.B
AU - Sadegh‐Nasseri, Scheherazade
AU - Dessi, Vitalia
AU - Sercarz, Eli E.
PY - 1986
Y1 - 1986
N2 - Immune responsiveness to lysozyme in H‐2b mice is under the control of H‐2‐linked Ir genes, with T suppressor (Ts) cells playing a dominant role in strains such as C57BL/6 (B6), C57BL/10 and A.BY. However, non‐H‐2‐genes were found to be capable of specific reversal of the effect of the H‐2‐linked genes in responsiveness to chicken lysozyme (HEL), but not to human lysozyme (HUL). Therefore, studies were performed to identify any lesion in the suppressor circuit in BALB.B. It was known that HUL‐induced suppressor cells could cross‐suppress the anti‐HEL response in B10.Q mice, which are responsive to HEL but nonresponsive to HUL. Similarly, BALB.B Ts cells were able to suppress the anti‐HEL response, using as T helper (Th) source a T cell line (BB‐l), derived from HEL‐primed BALB.B periaortic and inguinal lymph node cells. A protocol designed to examine the in vivo suppression by the use of HUL‐induced suppressor cells also demonstrated a significant suppression to the anti‐HEL response. Since the suppressive circuitry seemed intact in the BALB.B, the possibility was examined that a step in T‐B cell collaboration was more efficient in this strain than in the B6 nonresponder. With a B6‐derived HEL‐specific T cell line, BO1H, the B cell and antigen‐presenting (B/APC) populations from B6 required addition of concanavalin A supernatant for anti‐HEL antibody formation, whereas BALB.B B/APC were capable of responding to HEL in culture without the addition of concanavalin A supernatant. In agreement with this finding, when B/APC cell populations from BALB.B and B6 were compared for their extent of anti‐HEL responsiveness, as measured with BB‐1 Th cells, BALB.B B/APC populations responded significantly higher than B6 populations when the responses were activated by picogram/nanogram amounts of HEL. The response level of (BALB.B × B6)F1 B/APC measured in the same assay resembled that of B6. However, when HEL was used at the microgram level, both B6 and BALB.B strains responded equivalently. The above data are consistent with the expression of the reversing non‐H‐2 Ir gene(s) resulting from the balance of antigen presentation to Th and Ts cells in the H‐2b mouse. In the B6, processing and handling of antigen may be inefficient in activating response‐enhancing Th, and more effective in triggering Ts cells, while the reverse may be true for the BALB.B.
AB - Immune responsiveness to lysozyme in H‐2b mice is under the control of H‐2‐linked Ir genes, with T suppressor (Ts) cells playing a dominant role in strains such as C57BL/6 (B6), C57BL/10 and A.BY. However, non‐H‐2‐genes were found to be capable of specific reversal of the effect of the H‐2‐linked genes in responsiveness to chicken lysozyme (HEL), but not to human lysozyme (HUL). Therefore, studies were performed to identify any lesion in the suppressor circuit in BALB.B. It was known that HUL‐induced suppressor cells could cross‐suppress the anti‐HEL response in B10.Q mice, which are responsive to HEL but nonresponsive to HUL. Similarly, BALB.B Ts cells were able to suppress the anti‐HEL response, using as T helper (Th) source a T cell line (BB‐l), derived from HEL‐primed BALB.B periaortic and inguinal lymph node cells. A protocol designed to examine the in vivo suppression by the use of HUL‐induced suppressor cells also demonstrated a significant suppression to the anti‐HEL response. Since the suppressive circuitry seemed intact in the BALB.B, the possibility was examined that a step in T‐B cell collaboration was more efficient in this strain than in the B6 nonresponder. With a B6‐derived HEL‐specific T cell line, BO1H, the B cell and antigen‐presenting (B/APC) populations from B6 required addition of concanavalin A supernatant for anti‐HEL antibody formation, whereas BALB.B B/APC were capable of responding to HEL in culture without the addition of concanavalin A supernatant. In agreement with this finding, when B/APC cell populations from BALB.B and B6 were compared for their extent of anti‐HEL responsiveness, as measured with BB‐1 Th cells, BALB.B B/APC populations responded significantly higher than B6 populations when the responses were activated by picogram/nanogram amounts of HEL. The response level of (BALB.B × B6)F1 B/APC measured in the same assay resembled that of B6. However, when HEL was used at the microgram level, both B6 and BALB.B strains responded equivalently. The above data are consistent with the expression of the reversing non‐H‐2 Ir gene(s) resulting from the balance of antigen presentation to Th and Ts cells in the H‐2b mouse. In the B6, processing and handling of antigen may be inefficient in activating response‐enhancing Th, and more effective in triggering Ts cells, while the reverse may be true for the BALB.B.
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U2 - 10.1002/eji.1830160504
DO - 10.1002/eji.1830160504
M3 - Article
C2 - 2938974
AN - SCOPUS:0022577618
SN - 0014-2980
VL - 16
SP - 486
EP - 492
JO - European Journal of Immunology
JF - European Journal of Immunology
IS - 5
ER -