Suppressor cells induced by total lymphoid irradiation affect proliferation and lymphokine production of murine T helper cell clones

Abstract

A key response to antigen is the activation of helper T cells to release lymphokines which stimulate and effect the immune reaction. This T cell population can secrete many different factors with diverse, often multifunctional roles, such as amplifying T or B cell antigen responses or being effectors of cell mediated delayed type hypersensitivity. Among these lymphokines are gamma-interferon (gamma-IFN), interleukin-2 (IL-2), or T cell growth factor, and lymphotoxin (LT) which has cytotoxic activity against a variety of cells. Immune suppression in mice following total lymphoid irradiation (TLI) has been correlated with the presence in lympho-reticular tissues of an antigen non-specific, null suppressor cell. This study examined what effects radiation induced suppressor cells had upon the in vitro activation and lymphokine responses of the ovalbumin (OVA) specific T helper cell clone, 153E6, following antigen presentation. Splenocytes from TLI treated mice obtained early in the post-irradiation period exerted a pan-inhibitory effect upon OVA induced 153E6 proliferation and its concomitant release of gamma-IFN, LT, and IL-2. As the interval from irradiation increased, splenocytes from TLI treated mice showed persistent suppression of 153E6 proliferation and gamma-IFN release, but had rapidly diminishing effects on the T cell's capacity to produce LT and IL-2. These findings suggest that suppressor cells induced by TLI have a marked inhibitory effect in vivo upon T helper cell proliferative responses to antigen and the production of various T helper cell lymphokines necessary to mediate the immune response. Such processes could contribute to the immunosuppressive effects of extensive nodal irradiation.