Elimination of both CD4⁺ and CD8⁺ T cells but not B cells eliminates inflammation and prolongs the survival of TGFβ1-deficient mice

Transforming growth factor β1 (TGFβ1) is a potent negative immunoregulatory molecule. We have previously shown that the autoimmune-mediated weaning-age lethality of Tgfb1^-/- mice is reversed upon genetic combination with Scid or Rag null alleles. Here, we show that elimination of T but not B cells is sufficient for the reversal, but elimination of either CD4⁺ or CD8⁺ cells is not. Although elimination of B cells does not rescue TGFβ1-deficient animals from autoimmunity, B cells are hyperresponsive to LPS in the absence of TGFβ1. TGFβ1 deficiency leads to activation of CD8⁺ T cells as suggested by down-modulation of CD8 even in the absence of CD4⁺ T cells. This study provides evidence that both CD4⁺ and CD8⁺ T cells, but not B cells, have the ability to cause inflammation in the absence of TGFβ1. However, though TGFβ1-deficient B cells are hyperresponsive to stimulation, alone they are not sufficient to cause inflammation.