Fig. 1.

T cells prolong survival. (A) mSOD1^G93A/PU.1^−/− mice on a B6/SJL genetic background receiving CCR2^−/− BMT have a shorter survival time (133 ± 2 days, n = 10) than mSOD1^G93A/PU.1^−/− mice after WT BMT (141 ± 3 days, n = 12), and were similar to mSOD1^G93A/PU.1^+/− littermates (133 ± 2 days, n = 12; data not shown for clarity) and mSOD1^G93A/PU.1^−/− mice with mSOD1^G93A BMT (130 ± 2 days, n = 12). (B) Disease duration was attenuated in mSOD1^G93A/PU.1^−/− mice receiving CCR2^−/− BMT. Data for mSOD1^G93A/PU.1^+/− mice were eliminated for clarity but were similar to mSOD1^G93A/PU.1^−/− mice with mSOD1^G93A BMT (P = 0.55). (C) CD11b immunohistochemistry of morphologically activated microglia at end-stage disease in mSOD1^G93A/PU.1^+/− mice. (D) Following BMT with CCR2^−/− donor-derived cells, the CD11b signal from microglia of mSOD1^G93A/PU.1^−/− was reduced. (E) CD3+ T cells were observed in mSOD1^G93A/PU.1^+/− mice. (F) CD3+ T cells were absent in mSOD1^G93A/PU.1^−/− mice receiving CCR2^−/− BMT. (G) Survival times were shorter in mSOD1^G93A/RAG2^−/− mice, on a C57BL/6 genetic background, lacking functional T and B cells (145 ± 2 days, n = 14) than in mSOD1^G93A/RAG2^+/− littermates (161 ± 2 days, n = 13), but were prolonged following BMT (mSOD1^G93A: 164 ± 3 days, n = 10; WT: 161 ± 2 days, n = 10). RAG2^−/− BMT did not increase survival (148 ± 2 days, n = 10). Survival of mSOD1^G93A/RAG2^+/− mice were similar to mSOD1^G93A/RAG2^+/+ (160 ± 3 days, n = 20, P = 0.61). (H) Disease duration was shorter in mSOD1^G93A/RAG2^−/− mice than mSOD1^G93A/RAG2^+/− littermates, but was prolonged following BMT. (I) Disease progression in mSOD1^G93A/RAG2^−/− mice lacked the 4-week plateau of mSOD1^G93A/RAG2^+/− mice and was re-established after mSOD1^G93A BMT. *, Not different from mSOD1^G93A/PU.1^−/− mice with mSOD1^G93A BMT; ^‡different from mSOD1^G93A/PU.1^−/− mice with WT BMT; +different from mSOD^G93A/RAG2^+/−; #, not different from mSOD^G93A/RAG2^−/−. (Scale bars: C and D, 100 μm; E and F, 50 μm.)