Correction of antigen-specific T cell defects in aged murine gut-associated lymphoid tissues an immune intervention by combined adoptive transfer of an antigen-specific immunoregulatory CD4 T cell subset and interleukin 2 administration

Abstract

Gut-associated lymphoid tissues (GALT) from aged mice enterically immunized with Mycobacterium paratuberculosis protoplasmic antigen show hyperreactive humoral immune responses; this hyperresponsiveness can be corrected to a considerable extent, but not entirely, by systemic administration of interleukin 2 (IL 2) alone. The aim of the present study was to determine further whether the hyperreactivity in the antigen-specific humoral immune responses in aged GALT could be fully restored by adoptive transfer of in vitro expanded antigen-specific IL 2-dependent helper (CD4+VV-) T cells from GALT in conjunction with recombinant IL 2 administration. The results show that the age-associated hyperresponsiveness in gut mucosal antigen-specific humoral immune responses can be entirely corrected by adoptive transfer with the antigen-specific GALT T helper cells together with in vivo IL 2 administration. The mechanism of this restoration involves reversal of the decline in antigen-specific CD8+ suppressor T cell functions in aged GALT.