Fever and the immune response. The effects of physiological temperatures on primary murine splenic T-cell responses in vitro.

Abstract

Fever is a common sign of clinical disease but its biological purpose is unclear. Several cytokines mediate fever as well as the regulation of immune responses, and it was previously shown that murine thymocyte proliferative responses to IL-1 and IL-2 are exquisitely temperature-sensitive. The present studies were performed to determine whether such a high degree of temperature sensitivity was also a property of the primary in vitro immune responses of mature, murine splenic T cells. Using a physiological range of temperatures spanning those of normal skin (29 degrees C) to those of febrile core tissues (39 degrees C), primary murine spleen cell proliferative responses to either Con A, solid-phase anti-CD3 antibody, specific Ag, or allogenic cells were all found to display a high degree of temperature sensitivity. A similar pattern of strong temperature sensitivity was found for the capacity of primary MLR cultures to generate allospecific effector CTL. All of these forms of T-cell temperature sensitivity are expressed both in terms of the absolute degree of the response and in terms of its kinetics, the warmer temperatures up to 35 degrees C to 37 degrees C giving larger responses sooner than the lower physiological temperatures of 29 degrees C to 33 degrees C, at which these responses are markedly inhibited relative to those at 37 degrees C. In contrast, the effector cytolytic activity of a previously formed population of CTL is remarkably insensitive to the same temperature changes that strongly regulate the generation of those effector cells. The temperatures that usually define fever are those appropriate to the core tissues of a febrile animal, yet temperature changes in this range (37 degrees C-39 degrees C) had little stimulatory effect upon the T-cell responses studied, and were, in some cases, actually inhibitory. Temperature changes appropriate to the peripheral tissue temperatures in an animal becoming febrile (29 degrees C-37 degrees C) appear to be the ones that strongly regulate mature primary T-cell responses. These results suggest that one purpose of either fever or local tissue inflammation may be to temporarily ablate the cooler portions of normal thermal gradients, thereby selectively amplifying the emergence of T-cell immunity in peripheral tissues.