IMPAIRMENT OF ANTIGEN-SPECIFIC T-CELL PRIMING IN MICE LACKING CD40 LIGAND

LACK of functional expression of CD40 ligand (CD40L) on T cells result s in hyper-IgM syndrome (HIGM1), a human immunodeficiency associated w ith a severely impaired humoral immune response that is consistent wit h defects in B-cell responses(1-3). Patients also succumb to recurrent opportunistic infections such as Pneumocystis carinii and a Cryptospo ridial diarrhoea(4,5), suggesting that T-cell functions are also compr omised in these individuals, but so far this has not been explained. W e have previously shown that mice deficient for CD40L, like HIGM1 pati ents, show grossly abnormal humoral responses(6). Here we report that CD40L-deficient mice are defective in antigen-specific T-cell response s, Adoptively transferred antigen-specific CD4(+) T cells lacking CD40 L failed to expand upon antigen challenge of the recipients, showing t hat expression of CD40L on T cells is required for in vivo priming of CD4(+) T cells and therefore for the initiation of specific T-cell imm une responses.